Siga este enlace para ver otros tipos de publicaciones sobre el tema: Peptides Heparin Hormone receptors.
Artículos de revistas sobre el tema "Peptides Heparin Hormone receptors"
Crea una cita precisa en los estilos APA, MLA, Chicago, Harvard y otros
Consulte los 50 mejores artículos de revistas para su investigación sobre el tema "Peptides Heparin Hormone receptors".
Junto a cada fuente en la lista de referencias hay un botón "Agregar a la bibliografía". Pulsa este botón, y generaremos automáticamente la referencia bibliográfica para la obra elegida en el estilo de cita que necesites: APA, MLA, Harvard, Vancouver, Chicago, etc.
También puede descargar el texto completo de la publicación académica en formato pdf y leer en línea su resumen siempre que esté disponible en los metadatos.
Explore artículos de revistas sobre una amplia variedad de disciplinas y organice su bibliografía correctamente.
1
Suarez, Eloah Rabello, Helena Bonciani Nader, Maria Aparecida Silva Pinhal y Auro Del Giglio. "Selecting peptides for breast cancer treatment." Journal of Clinical Oncology 30, n.º 15_suppl (20 de mayo de 2012): e13016-e13016. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.e13016.
Texto completoResumen
e13016 Background: HER2 is a member of epidermal growth factor family of receptors that is an essential mediator of cell proliferation and differentiation. In breast cancer patients, HER2 overexpression is associated with aggressive disease, chemo and hormone therapy resistance and poor prognosis. Currently, a HER2 specific monoclonal antibody, trastuzumab, is in use as a treatment for these breast cancer cases; however, there are many reports of resistance to this treatment. As an alternative we have selected specific peptides to HER2 using a phage display technology. Methods: A cyclic 7 aminoacids random peptide library had been panned using an external domain of recombinant HER2. After each round of binding assays, peptides were sequenced and two were selected. Cellular viability, migration and apoptosis/necrosis induced by these peptides were evaluated using SKBR3 cells. Confocal microscopy was used to determine the peptides co-localization with acidic vesicles and heparan sulfate. Western blotting was performed to evaluated some cell signalling pathways induced by these peptides. Results: The peptides were able to reduce the cell viability and migration around 50% alone and 85% in association. Tavelorb was able to induce apoptosis/ necrosis in 70% of SKBR3 cells and when associated with Hercid, the effect has increased to 90%. These peptides co-localize with acidic vesicles around 40-50%. The peptides and trastuzumab co-localized with heparan sulfate around 70%. The association between Hercid and Tavelorb inhibits Akt (pSer473) and the proteins enrolled in this pathway, as GSK3 and the transcription factor c-myc, however Akt inhibition is not dependent of PTEN. In addition, this peptides decreases BCL-XL, and MCL-1, while enhance Bax. The most important effect of this peptides is the reduction in β-catenin expression. Interestingly, p53 is downregulated in the presence of trastuzumab showing a mechanism by some tumors could be resistant to this therapy. Conclusions: The association of peptides has a very effective antitumoral effect in vitro, and their action seems to be HS dependent. The data propose a potential use of these peptides as a future alternative for breast cancer treatment. Supported by FAPESP, CNPq, CAPES.
2
de Heuvel, Elaine, Laurie Wallace, Keith A. Sharkey y David L. Sigalet. "Glucagon-like peptide 2 induces vasoactive intestinal polypeptide expression in enteric neurons via phophatidylinositol 3-kinase-γ signaling". American Journal of Physiology-Endocrinology and Metabolism 303, n.º 8 (15 de octubre de 2012): E994—E1005. http://dx.doi.org/10.1152/ajpendo.00291.2012.
Texto completoResumen
Glucagon-like peptide 2 (GLP-2) is an enteroendocrine hormone trophic for intestinal mucosa; it has been shown to increase enteric neuronal expression of vasoactive intestinal polypeptide (VIP) in vivo. We hypothesized that GLP-2 would regulate VIP expression in enteric neurons via a phosphatidylinositol-3 kinase-γ (PI3Kγ) pathway. The mechanism of action of GLP-2 was investigated using primary cultures derived from the submucosal plexus (SMP) of the rat and mouse colon. GLP-2 (10−8 M) stimulation for 24 h increased the proportion of enteric neurons expressing VIP (GLP-2: 40 ± 6% vs. control: 22 ± 5%). GLP-2 receptor expression was identified by immunohistochemistry on neurons (HuC/D+) and glial cells (GFAP+) but not on smooth muscle or fibroblasts in culture. Over 1–4 h, GLP-2 stimulation of SMP increased phosphorylated Akt/Akt ratios 6.1-fold, phosphorylated ERK/ERK 2.5-fold, and p70S6K 2.2-fold but did not affect intracellular cAMP. PI3Kγ gene deletion or pharmacological blockade of PI3Kγ, mammalian target of rapamycin (mTOR), and MEK/ERK pathways blocked the increase in VIP expression by GLP-2. GLP-2 increased the expression of growth factors and their receptors in SMP cells in culture [IGF-1r (3.2-fold increase), EGFr (5-fold), and ErbB-2–4r (6- to 7-fold)] and ligands [IGF-I (1.5-fold), amphiregulin (2.5-fold), epiregulin (3.2-fold), EGF (7.5-fold), heparin-bound EGF (2.0-fold), β-cellulin (50-fold increase), and neuregulins 2–4 (300-fold increase) (by qRT-PCR)]. We conclude that GLP-2 acts on enteric neurons and glial cells in culture via a PI3Kγ/Akt pathway, stimulating neuronal differentiation via mTOR and ERK pathways, and expression of receptors and ligands for the IGF-I and ErbB pathways.
3
Hillhouse, E. W., H. Randeva, G. Ladds y D. Grammatopoulos. "Corticotropin-releasing hormone receptors". Biochemical Society Transactions 30, n.º 4 (1 de agosto de 2002): 428–32. http://dx.doi.org/10.1042/bst0300428.
Texto completoResumen
Corticotropin-releasing hormone (CRH) and related peptides (urocortins, sauvagine, urotensin) play a central role in the co-ordination of autonomic, behavioural, cardiovascular, immune and endocrine responses to stressful stimuli. Their actions are mediated through activation of two types of G-protein-coupled receptors encoded by separate genes. In this review we focus on the diverse structural and functional characteristics of the family of CRH-like peptides and their receptors.
4
Quittot, Noé, Phuong Trang Nguyen, Armelle Tchoumi Nerée, Marc P. Lussier y Steve Bourgault. "Identification of a conformational heparin-recognition motif on the peptide hormone secretin: key role for cell surface binding". Biochemical Journal 474, n.º 13 (26 de junio de 2017): 2249–60. http://dx.doi.org/10.1042/bcj20170035.
Texto completoResumen
Secretin is a peptide hormone that exerts pleiotropic physiological functions by specifically binding to its cognate membrane-bound receptor. The membrane catalysis model of peptide–receptor interactions states that soluble peptidic ligands initially interact with the plasma membrane. This interaction increases the local concentration and structures the peptide, enhancing the rate of receptor binding. However, this model does not consider the dense network of glycosaminoglycans (GAGs) at the surface of eukaryotic cells. These sulfated polysaccharide chains are known to sequester numerous proteic signaling molecules. In the present study, we evaluated the interaction between the peptide hormone secretin and sulfated GAGs and its contribution to cell surface binding. Using GAG-deficient cells and competition experiments with soluble GAGs, we observed by confocal microscopy and flow cytometry that GAGs mediate the sequestration of secretin at the cell surface. Isothermal titration calorimetry and surface plasmon resonance revealed that secretin binds to heparin with dissociation constants ranging between 0.9 and 4 μM. By designing secretin derivatives with a restricted conformational ensemble, we observed that this interaction is mediated by the presence of a specific conformational GAG-recognition motif that decorates the surface of the peptide upon helical folding. The present study identifies secretin as a novel GAG-binding polypeptide and opens new research direction on the functional role of GAGs in the biology of secretin.
5
Ghigo, E., E. Arvat, G. Muccioli y F. Camanni. "Growth hormone-releasing peptides". European Journal of Endocrinology 136, n.º 5 (mayo de 1997): 445–60. http://dx.doi.org/10.1530/eje.0.1360445.
Texto completoResumen
Abstract Growth hormone-releasing peptides (GHRPs) are synthetic, non-natural peptides endowed with potent stimulatory effects on somatotrope secretion in animals and humans. They have no structural homology with GHRH and act via specific receptors present either at the pituitary or the hypothalamic level both in animals and in humans. The GHRP receptor has recently been cloned and, interestingly, it does not show sequence homology with other G-protein-coupled receptors known so far. This evidence strongly suggests the existence of a natural GHRP-like ligand which, however, has not yet been found. The mechanisms underlying the GHRP effect are still unclear. At present, several data favor the hypothesis that GHRPs could act by counteracting somatostatinergic activity both at the pituitary and the hypothalamic level and/or, at least partially, via a GHRH-mediated mechanism. However, the possibility that GHRPs act via an unknown hypothalamic factor (U factor) is still open. GHRP-6 was the first hexapeptide to be extensively studied in humans. More recently, a heptapeptide, GHRP-1, and two other hexapeptides, GHRP-2 and Hexarelin, have been synthesized and are now available for human studies. Moreover, non-peptidyl GHRP mimetics have been developed which act via GHRP receptors and their effects have been clearly demonstrated in animals and in humans in vivo. Among non-peptidyl GHRPs, MK-0677 seems the most interesting molecule. The GH-releasing activity of GHRPs is marked and dose-related after intravenous, subcutaneous, intranasal and even oral administration. The effect of GHRPs is reproducible and undergoes partial desensitization, more during continuous infusion, less during intermittent administration; in fact, prolonged administration of GHRPs increases IGF-I levels both in animals and in humans. The GH-releasing effect of GHRPs does not depend on sex but undergoes age-related variations. It increases from birth to puberty, persists at a similar level in adulthood and decreases thereafter. By the sixth decade of life, the activity of GHRPs is reduced but it is still marked and higher than that of GHRH. The GH-releasing activity of GHRPs is synergistic with that of GHRH, is not affected by opioid receptor antagonists, such as naloxone, and is only blunted by inhibitory influences, including neurotransmitters, glucose, free fatty acids, glucocorticoids, recombinant human GH and even exogenous somatostatin, which are known to almost abolish the effect of GHRH. GHRPs maintain their GH-releasing effect in somatotrope hypersecretory states such as in acromegaly, anorexia nervosa and hyperthyroidism. On the other hand, their good GH-releasing activity has been shown in some but not in other somatotrope hyposecretory states. In fact, reduced GH responses after GHRP administration have been reported in idiopathic GH deficiency as well as in idiopathic short stature, in obesity and in hypothyroidism, while in patients with pituitary stalk disconnection or Cushing's syndrome the somatotrope responsiveness to GHRPs is almost absent. In short children an increase in height velocity has also been reported during chronic GHRP treatment. Thus, based on their marked GH-releasing effect even after oral administration, GHRPs offer their own clinical usefulness for treatment of some GH hyposecretory states. European Journal of Endocrinology 136 445–460
6
Sehgal, I., J. Bailey, K. Hitzemann, M. R. Pittelkow y N. J. Maihle. "Epidermal growth factor receptor-dependent stimulation of amphiregulin expression in androgen-stimulated human prostate cancer cells." Molecular Biology of the Cell 5, n.º 3 (marzo de 1994): 339–47. http://dx.doi.org/10.1091/mbc.5.3.339.
Texto completoResumen
Amphiregulin is a heparin-binding epidermal growth factor (EGF)-related peptide that binds to the EGF receptor (EGF-R) with high affinity. In this study, we report a role for amphiregulin in androgen-stimulated regulation of prostate cancer cell growth. Androgen is known to enhance EGF-R expression in the androgen-sensitive LNCaP human prostate carcinoma cell line, and it has been suggested that androgenic stimuli may regulate proliferation, in part, through autocrine mechanisms involving the EGF-R. In this study, we demonstrate that LNCaP cells express amphiregulin mRNA and peptide and that this expression is elevated by androgenic stimulation. We also show that ligand-dependent EGF-R stimulation induces amphiregulin expression and that androgenic effects on amphiregulin synthesis are mediated through this EGF-R pathway. Parallel studies using the estrogen-responsive breast carcinoma cell line, MCF-7, suggest that regulation of amphiregulin by estrogen may also be mediated via an EGF-R pathway. In addition, heparin treatment of LNCaP cells inhibits androgen-stimulated cell growth further suggesting that amphiregulin can mediate androgen-stimulated LNCaP proliferation. Together, these results implicate an androgen-regulated autocrine loop composed of amphiregulin and its receptor in prostate cancer cell growth and suggest that the mechanism of steroid hormone regulation of amphiregulin synthesis may occur through androgen upregulation of the EGF-R and subsequent receptor-dependent pathways.
7
Khomutov, А. Е., А. V. Deryugina, А. S. Lizunova y Z. V. Bobrova. "Heparin sensitization of fentanyl initiated mu-receptors". JOURNAL of SIBERIAN MEDICAL SCIENCES, n.º 1 (2021): 20–32. http://dx.doi.org/10.31549/2542-1174-2021-1-20-32.
Texto completoResumen
Heparin is an anticoagulant widely used in clinical practice. In addition to anticoagulant activity, heparin has a cytostatic, bacteriostatic, antilipemic, radioprotective effect, and exhibits antiallergic and hypotensive action. Heparin modulates cardiotropic, neurotropic, antihypoxic, anti-ischemic properties of regulatory peptides and pharmacological agents used in pain relief and anesthesia. At the same time, there is very little information about the antinociceptive effect of heparin. The aim of this work is to study the effect of heparin in combination with the opioid agonist fentanyl on mu-opioid receptors at the spinal and supraspinal levels. In experiments on laboratory rats, it was established that heparin, when pre-administered and combined with fentanyl, increases the latency in the tail flick test and the paw licking test. Naloxone, an opioid receptor antagonist, reduces antinociceptive efficacy of the studied compounds. Protamine sulfate also reduces the level of heparin sensitization of opioid receptors. Thus, the obtained data allow us to speak about the sensitizing effect of heparin on initiated by an agonist mu-opioid receptors at the spinal and supraspinal levels.
8
Silvestri, Laura, Alessia Pagani, Antonella Nai y Clara Camaschella. "Novel Insights Into Systemic Iron Regulation". Blood 132, Supplement 1 (29 de noviembre de 2018): SCI—1—SCI—1. http://dx.doi.org/10.1182/blood-2018-99-109518.
Texto completoResumen
Abstract Iron, an essential element in mammals, is absorbed by duodenal enterocytes, enters the circulation through the iron exporter ferroportin, (FPN), circulates bound to transferrin and is uptaken through Transferrin Receptor 1. If in excess, iron is stored in macrophages and hepatocytes and released when needed. To maintain systemic iron homeostasis and to avoid the formation of "non transferrin bound iron" (NTBI), a highly reactive form which causes organ damage, the liver synthetizes hepcidin that, binding FPN, blocks iron export to the circulation. Hepcidin integrates signals from body iron, erythropoiesis and inflammatory cytokines. Defective hepcidin production causes iron overload and organ failure in Hereditary Hemochromatosis and Thalassemia; hepcidin excess leads to anemia in Iron Refractory iron Deficiency Anemia (IRIDA) and Anemia of Inflammation (AI). In hepatocytes hepcidin is under the control of the BMP-SMAD pathway, which is activated in a paracrine manner by BMP2 and BMP6 produced by liver sinusoidal endothelial cells. BMP2 maintains hepcidin basal levels, while BMP6 controls its expression in response to iron. The two ligands have different affinity for BMP type I receptors ALK2 and ALK3, suggesting two distinct branches of the hepcidin activation pathway. This possibility is consistent with the non-redundant function of BMP2 and BMP6, the different iron phenotype of hepatocyte-conditional ALK2 and ALK3 KO mice and the residual ability of BMP6 to activate hepcidin in hemochromatosis mice. Moreover ALK2, but not ALK3, is inhibited by the immunophilin FKBP12 in the absence of ligands. The BMP pathway activation depends upon the coreceptor hemojuvelin (HJV), the MHC class I protein HFE and the second transferrin receptor (TFR2). Mutations of all these proteins lead to decreased hepcidin expression in hemochromatosis. Hepcidin expression is inhibited in iron deficiency, hypoxia and when erythropoiesis is increased. Inhibitors are the liver transmembrane serine protease TMPRSS6, whose genetic inactivation causes IRIDA, and the erythroid hormone erythroferrone (ERFE), which is released by erythropoietin-stimulated erythroblasts. The mechanism of hepcidin inhibition by ERFE is unclear; still to allow ERFE function the BMP-SMAD pathway has not to be hyperactive. Intriguingly, both iron deficiency and erythropoiesis require epigenetic modifications at the hepcidin locus with HDAC3-dependent reversible loss of H3K9ac and H3K4me3. Hepcidin also acts as an antimicrobial peptide since its expression, increased by proinflammatory cytokines, such as IL6 through JAK2-STAT3 signaling, restricts iron availability for microbial growth. This first-line of defense against infections negatively influences erythropoiesis since chronic hepcidin activation causes AI. Despite persistent JAK2-STAT3 activation, inhibition of the BMP-SMAD pathway reduces hepcidin activation in AI experimental rodent models, suggesting that hepcidin activation in inflammation requires a functional BMP-SMAD pathway. Independently from hepcidin, inflammation also reduces FPN mRNA levels, favoring macrophage iron sequestration. The identification of hepcidin-ferroportin axis molecular players has translational implications. In primary and secondary iron overload hepcidin agonists (hepcidin peptides or mimics, agents that inhibit the hepcidin inhibitor TMPRSS6 and likely the ALK2-inhibitor FKBP12) and ferroportin inhibitors are potentially useful to prevent iron overload and/or to favor iron redistribution to macrophages. In case of AI, hepcidin antagonists (including anti-hepcidin, anti-HJV and anti-BMP6 monoclonal antibodies, L-enantiomeric oligonucleotides targeting hepcidin, siRNA against hepcidin, non-anticoagulant heparins, the ALK2 inhibitor momelotinib) might improve erythropoiesis increasing iron availability. The effect of some agents that have now entered the clinical phase will become apparent in the coming years. Disclosures Camaschella: vifor Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees.
9
Kawada, Tsuyoshi, Toshio Sekiguchi, Tsubasa Sakai, Masato Aoyama y Honoo Satake. "Neuropeptides, Hormone Peptides, and Their Receptors inCiona intestinalis:An Update". Zoological Science 27, n.º 2 (febrero de 2010): 134–53. http://dx.doi.org/10.2108/zsj.27.134.
Texto completo
10
IRWIN, DAVID M. "Evolution of Hormone Function: Proglucagon-derived Peptides and Their Receptors". BioScience 55, n.º 7 (2005): 583. http://dx.doi.org/10.1641/0006-3568(2005)055[0583:eohfpp]2.0.co;2.
Texto completo
11
Motomitsu, Ayane, Shinichiro Sawa y Takashi Ishida. "Plant peptide hormone signalling". Essays in Biochemistry 58 (15 de septiembre de 2015): 115–31. http://dx.doi.org/10.1042/bse0580115.
Texto completoResumen
The ligand–receptor-based cell-to-cell communication system is one of the most important molecular bases for the establishment of complex multicellular organisms. Plants have evolved highly complex intercellular communication systems. Historical studies have identified several molecules, designated phytohormones, that function in these processes. Recent advances in molecular biological analyses have identified phytohormone receptors and signalling mediators, and have led to the discovery of numerous peptide-based signalling molecules. Subsequent analyses have revealed the involvement in and contribution of these peptides to multiple aspects of the plant life cycle, including development and environmental responses, similar to the functions of canonical phytohormones. On the basis of this knowledge, the view that these peptide hormones are pivotal regulators in plants is becoming increasingly accepted. Peptide hormones are transcribed from the genome and translated into peptides. However, these peptides generally undergo further post-translational modifications to enable them to exert their function. Peptide hormones are expressed in and secreted from specific cells or tissues. Apoplastic peptides are perceived by specialized receptors that are located at the surface of target cells. Peptide hormone–receptor complexes activate intracellular signalling through downstream molecules, including kinases and transcription factors, which then trigger cellular events. In this chapter we provide a comprehensive summary of the biological functions of peptide hormones, focusing on how they mature and the ways in which they modulate plant functions.
12
Zoumakis, E., D. K. Grammatopoulos y G. P. Chrousos. "Corticotropin-releasing hormone receptor antagonists". European Journal of Endocrinology 155, suppl_1 (noviembre de 2006): S85—S91. http://dx.doi.org/10.1530/eje.1.02259.
Texto completoResumen
Corticotropin-releasing hormone (CRH), CRH-related peptides, and CRH receptors play major roles in coordinating the behavioral, endocrine, autonomic, and immune responses to stress. The wide influence of the CRH system on physiological processes in both brain and periphery implicates the respective peptides in the pathophysiology of numerous disorders characterized by dysregulated stress responses. The potential use of CRH antagonists is presently under intense investigation. Selective antagonists have been used experimentally to elucidate the role of CRH-related peptides in disease processes, such as anxiety and depression, sleep disorders, addictive behavior, inflammatory disorders, acute and chronic neurodegeneration, and preterm labor.
13
Wheatley, M., S. R. Hawtin, V. J. Wesley, H. C. Howard, J. Simms, A. Miles, K. McEwan y R. A. Parslow. "Agonist binding to peptide hormone receptors". Biochemical Society Transactions 31, n.º 1 (1 de febrero de 2003): 35–39. http://dx.doi.org/10.1042/bst0310035.
Texto completoResumen
A fundamental issue in molecular pharmacology is to define how agonist–receptor interaction differs from that of antagonist–receptor interaction. The V1a vasopressin receptor (V1aR) is a member of a family of related G-protein-coupled receptors (GPCRs) that are activated by vasopressin, oxytocin (OT) and related peptides. A segment of the N-terminus that was required for agonist binding, but not antagonist binding, was identified by characterizing truncated V1aR constructs. Site-directed mutagenesis revealed that a single residue (Arg46) was critical for agonist binding and receptor activation. The N-terminus of the related OT receptor (OTR) could recover agonist binding in a chimaeric OTRN–V1aR construct. Furthermore, Arg34 of the human OTR, which corresponds to Arg46 of the rat V1aR, provided agonist-specific binding epitopes in the OTR, indicating a conserved function of this locus throughout this GPCR subfamily. Mutation of Arg46 revealed that high-affinity agonist binding had an absolute requirement for arginine at this position.
14
Slominski, Andrzej, Jacobo Wortsman, Thomas Luger, Ralf Paus y Samuel Solomon. "Corticotropin Releasing Hormone and Proopiomelanocortin Involvement in the Cutaneous Response to Stress". Physiological Reviews 80, n.º 3 (1 de julio de 2000): 979–1020. http://dx.doi.org/10.1152/physrev.2000.80.3.979.
Texto completoResumen
The skin is a known target organ for the proopiomelanocortin (POMC)-derived neuropeptides α-melanocyte stimulating hormone (α-MSH), β-endorphin, and ACTH and also a source of these peptides. Skin expression levels of the POMC gene and POMC/corticotropin releasing hormone (CRH) peptides are not static but are determined by such factors as the physiological changes associated with hair cycle (highest in anagen phase), ultraviolet radiation (UVR) exposure, immune cytokine release, or the presence of cutaneous pathology. Among the cytokines, the proinflammatory interleukin-1 produces important upregulation of cutaneous levels of POMC mRNA, POMC peptides, and MSH receptors; UVR also stimulates expression of all the components of the CRH/POMC system including expression of the corresponding receptors. Molecular characterization of the cutaneous POMC gene shows mRNA forms similar to those found in the pituitary, which are expressed together with shorter variants. The receptors for POMC peptides expressed in the skin are functional and include MC1, MC5 and μ-opiate, although most predominant are those of the MC1 class recognizing MSH and ACTH. Receptors for CRH are also present in the skin. Because expression of, for example, the MC1 receptor is stimulated in a similar dose-dependent manner by UVR, cytokines, MSH peptides or melanin precursors, actions of the ligand peptides represent a stochastic (predictable) nonspecific response to environmental/endogenous stresses. The powerful effects of POMC peptides and probably CRH on the skin pigmentary, immune, and adnexal systems are consistent with stress-neutralizing activity addressed at maintaining skin integrity to restrict disruptions of internal homeostasis. Hence, cutaneous expression of the CRH/POMC system is highly organized, encoding mediators and receptors similar to the hypothalamic-pituitary-adrenal (HPA) axis. This CRH/POMC skin system appears to generate a function analogous to the HPA axis, that in the skin is expressed as a highly localized response which neutralizes noxious stimuli and attendant immune reactions.
15
Sehadova, Hana, Yoko Takasu, Anna Zaloudikova, Yu-Hsien Lin, Ivo Sauman, Hideki Sezutsu, Lenka Rouhova, Dalibor Kodrik y Michal Zurovec. "Functional Analysis of Adipokinetic Hormone Signaling in Bombyx mori". Cells 9, n.º 12 (11 de diciembre de 2020): 2667. http://dx.doi.org/10.3390/cells9122667.
Texto completoResumen
Insect adipokinetic hormones (AKHs) are short peptides produced in the corpora cardiaca and are responsible for mobilizing energy stores from the fat body to the hemolymph. Three related peptides, AKH1, AKH2, and AKH/corazonin-related peptide (ACP) as well as three AKH receptors have been reported in Bombyx mori. AKH1 and AKH2 are specific for the AKHR1 receptor, whereas ACP interacts with the other two AKHRs. To assess the effect of the two silkworm AKHs and ACP in the regulation of energy homeostasis we examined the expression pattern of the three peptides and their receptors as well as their effect on the level of carbohydrates and lipids in the hemolymph. Our results support the hypothesis that only AKH1 and AKH2 peptides together with the AKHR1 receptor are involved in the maintenance of energy homeostasis. Because Bombyx AKHR1 (BmAKHR1) seems to be a true AKHR we generated its mutation. The BmAKHR1 mutant larvae display significantly lower carbohydrate and lipid levels in the hemolymph and reduced sensitivity to starvation. Our study clarifies the role of BmAKHR1 in energy homeostasis.
16
Saikali, Michael Fadi y Carolyn L. Cummins. "Quantifying the Protein Levels of All Nuclear Hormone Receptors by Mass Spectrometry". Journal of the Endocrine Society 5, Supplement_1 (1 de mayo de 2021): A815. http://dx.doi.org/10.1210/jendso/bvab048.1660.
Texto completoResumen
Abstract Nuclear Receptors (NRs) are a family of ligand-activated transcription factors that control the expression of genes involved in a wide range of physiological processes. An atlas detailing the expression of all NRs at the mRNA level was completed in 2006 using quantitative PCR [Bookout et al. Cell 2006]. The comparative measurement of NRs at the protein level, however, has been hindered by the poor quality of commercially available antibodies, as well as the absence of a high throughput method for quantitation. To address this need, we are developing a mass spectrometry-based targeted proteomic assay to quantify the absolute amounts of NR protein in a panel of mouse tissues. NRs were overexpressed in HEK293 cells by transient transfection and protein was isolated. The cell lysates were digested with a combination of trypsin and Lys-C following the Multi-Enzyme Digestion Filter Aided Sample Preparation protocol. The peptides were desalted using an in-house made C18 tip, separated on an EASY-Spray C18 column (75 um x 50 cm, 3Å), and analyzed on a Thermo QExactive HF in Top20 data-dependent acquisition mode. Protein identifications were made using MaxQuant software, and the identifications were mined for members of the NR family. The NR peptides detected were searched against an in silico generated list of optimal NR peptides (filtered for uniqueness, length, absence of post translational modifications, and conservation between human and mouse). The matching peptides were validated by parallel reaction monitoring (PRM) and purchased as synthetic isotopes with a heavy terminal arginine or lysine. Peptide linearity, and lower limits of detection (LLOD) were estimated by spiking digests from a C57Bl/6 mouse liver lysate with increasing amounts of the labeled peptides and analyzing by PRM. Peptides that displayed non-linear behavior were excluded for quantitation. The LLOD were between 100 amol and 1.5 fmol on column. A test panel of tissues (cerebrum, hippocampus, cerebellum, liver, spleen, brown/white adipose, and kidney) showed that we could detect endogenous expression of NRs. To date, we have purchased and validated peptides for 44 of the 49 receptors. We used this assay to quantify the changes in NR protein expression in mouse livers in response to 16 hours of fasting. We found significant changes in the nuclear expression of CAR (3.1-fold increase), RXRβ (1.8-fold increase), SHP (3.9-fold decrease) and RARβ (2.0-fold decrease) in the fasted vs. fed state. Increased CAR activity with fasting was further supported by label-free quantitative proteomics on the same lysates which revealed 210 differentially expressed proteins (2-fold change, p<0.05), with 61 (29%) identified as known CAR target genes. Once complete, this assay will provide researchers with a robust quantitative tool to investigate changes in NR protein expression that will be widely applicable to endocrine research.
17
Lin, Xinwei, Carla J. Otto, Rodolfo Cardenas y Richard E. Peter. "Somatostatin family of peptides and its receptors in fish". Canadian Journal of Physiology and Pharmacology 78, n.º 12 (1 de diciembre de 2000): 1053–66. http://dx.doi.org/10.1139/y00-100.
Texto completoResumen
Somatostatin (SRIF or SS) is a phylogenetically ancient, multigene family of peptides. SRIF-14 is conserved with identical primary structure in species of all classes of vertebrates. The presence of multiple SRIF genes has been demonstrated in a number of fish species and could extend to tetrapods. Three distinct SRIF genes have been identified in goldfish. One of these genes, which encodes [Pro2]SRIF-14, is also present in sturgeon and African lungfish, and is closely associated with amphibian [Pro2,Met13]SRIF-14 gene and mammalian cortistatin gene. The post-translational processing of SRIF precursors could result in multiple forms of mature SRIF peptides, with differential abundance and tissue- or cell type-specific patterns. The main neuroendocrine role of SRIF-14 peptide that has been determined in fish is the inhibition of pituitary growth hormone secretion. The functions of SRIF-14 variant or larger forms of SRIF peptide and the regulation of SRIF gene expression remain to be explored. Type 1 and type 2 SRIF receptors have been identified from goldfish and a type 3 SRIF receptor has been identified from an electric fish. Fish SRIF receptors display considerable homology with mammalian counterparts in terms of primary structure and negative coupling to adenylate cyclase. Although additional types of receptors remain to be determined, identification of the multiple gene family of SRIF peptides and multiple types of SRIF receptors opens a new avenue for the study of physiological roles of SRIF, and the molecular and cellular mechanisms of SRIF action in fish.Key words: somatostatin, somatostatin receptor, growth hormone, fish.
18
Majzoub, Joseph A. "Corticotropin-releasing hormone physiology". European Journal of Endocrinology 155, suppl_1 (noviembre de 2006): S71—S76. http://dx.doi.org/10.1530/eje.1.02247.
Texto completoResumen
Corticotropin-releasing hormone (CRH), also known as corticotropin-releasing factor, is a highly conserved peptide hormone comprising 41 amino acid residues. Its name derives from its role in the anterior pituitary, where it mediates the release of corticotropin (ACTH) leading to the release of adrenocortical steroids. CRH is the major hypothalamic activator of the hypothalamic–pituitary–adrenal (HPA) axis. Major functions of the HPA include: (i) influencing fetal development of major organ systems including lung, liver, and gut, (ii) metabolic functions, including the maintenance of normal blood glucose levels during the fasting state via glycogenolysis and gluconeogenesis, (iii) modulation of immune function, and (iv) maintenance of cardiovascular tone. In addition, CRH, acting both directly and via the HPA, has a role in regulating several neuroendocrine functions including behavior, food intake, reproduction, growth, immune function, and autonomic function. CRH has been localized to the paraventricular nucleus (PVN) of the hypothalamus, which projects to the median eminence and other hypothalamic and midbrain targets. The CRH gene is composed of two exons. The CRH promoter contains a cAMP-response element, and the intron contains a restrictive element-1/neuron restrictive silencing element (RE-1/NRSE) sequence. Recently, a family of CRH-related peptides, termed the urocortins, has been identified. These peptides probably play a role in integrating multiple aspects of the stress-response, although their functions are largely unknown. Both CRH and the urocortins interact with two transmembrane G-protein-coupled cell surface receptors, CRH-R1, and CRH-R2, which differ in their patterns of tissue distribution. In addition, the binding affinities for CRH and the urocortins to the two receptors differ considerably, and may contribute to the different actions of these peptides.
19
Müller, Eugenio E., Vittorio Locatelli y Daniela Cocchi. "Neuroendocrine Control of Growth Hormone Secretion". Physiological Reviews 79, n.º 2 (1 de abril de 1999): 511–607. http://dx.doi.org/10.1152/physrev.1999.79.2.511.
Texto completoResumen
The secretion of growth hormone (GH) is regulated through a complex neuroendocrine control system, especially by the functional interplay of two hypothalamic hypophysiotropic hormones, GH-releasing hormone (GHRH) and somatostatin (SS), exerting stimulatory and inhibitory influences, respectively, on the somatotrope. The two hypothalamic neurohormones are subject to modulation by a host of neurotransmitters, especially the noradrenergic and cholinergic ones and other hypothalamic neuropeptides, and are the final mediators of metabolic, endocrine, neural, and immune influences for the secretion of GH. Since the identification of the GHRH peptide, recombinant DNA procedures have been used to characterize the corresponding cDNA and to clone GHRH receptor isoforms in rodent and human pituitaries. Parallel to research into the effects of SS and its analogs on endocrine and exocrine secretions, investigations into their mechanism of action have led to the discovery of five separate SS receptor genes encoding a family of G protein-coupled SS receptors, which are widely expressed in the pituitary, brain, and the periphery, and to the synthesis of analogs with subtype specificity. Better understanding of the function of GHRH, SS, and their receptors and, hence, of neural regulation of GH secretion in health and disease has been achieved with the discovery of a new class of fairly specific, orally active, small peptides and their congeners, the GH-releasing peptides, acting on specific, ubiquitous seven-transmembrane domain receptors, whose natural ligands are not yet known.
20
Boutin, Jean A., Thomas Suply, Valérie Audinot, Marianne Rodriguez, Philippe Beauverger, Jean-Paul Nicolas, Jean-Pierre Galizzi y Jean-Luc Fauchère. "Melanin-concentrating hormone and its receptors: state of the art". Canadian Journal of Physiology and Pharmacology 80, n.º 5 (1 de mayo de 2002): 388–95. http://dx.doi.org/10.1139/y02-056.
Texto completoResumen
Melanin-concentrating hormone (MCH) is a cyclic neuropeptide of nineteen amino acids in mammals. Its involvement in the feeding behaviour has been well established during the last few years. A first receptor subtype, now termed MCH1R, was discovered in 1999, following the desorphanisation of the SLC1 orphan receptor, using either reverse pharmacology or systematic screening of agonist candidates. A second MCH receptor, MCH2R, has been discovered recently, by several groups working on data mining of genomic banks. The molecular pharmacology of these two receptors is only described on the basis of the action of peptides derived from MCH. The present review tentatively summarizes the knowledge on these two receptors and presents the first attempts to discover new classes of antagonists that might have major roles in the control of obesity and feeding behaviour.Key words: melanin-concentrating hormone, melanin-concentrating hormone receptor, SLC-1, food intake, obesity.
21
Muff, Roman, Walter Born y Jan A. Fischer. "Calcitonin, calcitonin gene-related peptide, adrenomedullin and amylin: homologous peptides, separate receptors and overlapping biological actions". European Journal of Endocrinology 133, n.º 1 (julio de 1995): 17–20. http://dx.doi.org/10.1530/eje.0.1330017.
Texto completoResumen
Muff R, Born W, Fischer JA. Calcitonin, calcitonin gene-related peptide, adrenomedullin and amylin: homologous peptides, separate receptors and overlapping biological actions. Eur J Endocrinol 1995;133:17–20. ISSN 0804–4643 Calcitonin, calcitonin gene-related peptide, adrenomedullin and amylin are structurally related peptides with N-terminal 6–7 amino acid ring structures linked by a disulfide bridge and with amidated C-termini. Among the related bioactive peptides, the structures of the calcitonin receptor and subtypes thereof have been identified so far through molecular cloning. Cross-reaction between receptors of calcitonin, calcitonin gene-related peptide, adrenomedullin and amylin, as well as overlapping biological actions, anticipate that the respective receptors belong to a family of G-protein-coupled receptors that include those of parathyroid hormone, secretin and vasointestinal peptide. Jan A Fischer, Klinik Balgrist, Forchstrasse 340, CH-8008 Zurich, Switzerland
22
Coste, S. "Corticotropin-Releasing Hormone-Related Peptides and Receptors Emergent Regulators of Cardiovascular Adaptations to Stress". Trends in Cardiovascular Medicine 12, n.º 4 (mayo de 2002): 176–82. http://dx.doi.org/10.1016/s1050-1738(02)00157-3.
Texto completo
23
Hamy, François, Nicole Helbecque y Jean-Pierre Henichart. "Comparison between synthetic nuclear localization signal peptides from the steroid/thyroid hormone receptors superfamily". Biochemical and Biophysical Research Communications 182, n.º 1 (enero de 1992): 289–93. http://dx.doi.org/10.1016/s0006-291x(05)80143-3.
Texto completo
24
Ben-Menahem, David. "GnRH-Related Neurohormones in the Fruit Fly Drosophila Melanogaster". International Journal of Molecular Sciences 22, n.º 9 (10 de mayo de 2021): 5035. http://dx.doi.org/10.3390/ijms22095035.
Texto completoResumen
Genomic and phylogenetic analyses of various invertebrate phyla revealed the existence of genes that are evolutionarily related to the vertebrate’s decapeptide gonadotropin-releasing hormone (GnRH) and the GnRH receptor genes. Upon the characterization of these gene products, encoding peptides and putative receptors, GnRH-related peptides and their G-protein coupled receptors have been identified. These include the adipokinetic hormone (AKH) and corazonin (CRZ) in insects and their cognate receptors that pair to form bioactive signaling systems, which network with additional neurotransmitters/hormones (e.g., octopamine and ecdysone). Multiple studies in the past 30 years have identified many aspects of the biology of these peptides that are similar in size to GnRH and function as neurohormones. This review briefly describes the main activities of these two neurohormones and their receptors in the fruit fly Drosophila melanogaster. The similarities and differences between Drosophila AKH/CRZ and mammalian GnRH signaling systems are discussed. Of note, while GnRH has a key role in reproduction, AKH and CRZ show pleiotropic activities in the adult fly, primarily in metabolism and stress responses. From a protein evolution standpoint, the GnRH/AKH/CRZ family nicely demonstrates the developmental process of neuropeptide signaling systems emerging from a putative common ancestor and leading to divergent activities in distal phyla.
25
Dietrich, Jean-Bernard. "AR4-2J cells: A model to study polypeptide hormone receptors". Bioscience Reports 16, n.º 4 (1 de agosto de 1996): 273–88. http://dx.doi.org/10.1007/bf01855012.
Texto completoResumen
The AR4-2J cell line is derived from a transplantable tumour of the exocrine rat pancreas. Acinar in origin, this cell line contains significant amounts of amylase and can be grown in continuous culture. Many in vitro studies have been done using these cells; these studies were often complemented with in vivo experiments on animals. Particularly, many polypeptide hormones interacting with specific receptors located on the cell membrane have been analysed. The accurate knowledge of the hormone-receptor interactions has allowed to design interesting analogs of these hormones. In several cases, these compounds are powerful antagonists and are able to control cell proliferation induced by the corresponding polypeptide hormones. Other cell lines are useful to understand human pancreatic cancer. These human cell lines (Capan-1, Panc-1 for example) are of ductal origin and differ from AR4-2J cells, especially regarding the distribution of several polypeptide hormone and growth factor receptors. Both models are important for basic studies of neuropeptides, gastrointestinal peptides and their receptors, as well as for a better understanding of the underlying mechanisms of human pancreatic cancer.
26
Tello, Javier A., Jean E. Rivier y Nancy M. Sherwood. "Tunicate Gonadotropin-Releasing Hormone (GnRH) Peptides Selectively Activate Ciona intestinalis GnRH Receptors and the Green Monkey Type II GnRH Receptor". Endocrinology 146, n.º 9 (1 de septiembre de 2005): 4061–73. http://dx.doi.org/10.1210/en.2004-1558.
Texto completoResumen
Abstract In vertebrates, GnRH binds to its receptor and stimulates predominantly Gq/11-mediated signal transduction in gonadotropes. However, little is known about the GnRH receptor and its signaling pathway in tunicates, a group that arose before the vertebrates. Although tunicates have had duplications of a few genes in the last 600 million years, the early vertebrates had duplications of the full genome. Also unknown is the nature of GnRH signaling in the tunicate, which lacks both a pituitary gland and sex steroids. However, we know that tunicates have GnRH peptides because we previously reported six GnRH peptides encoded within the tunicate genome of Ciona intestinalis. Here we clone and sequence cDNAs for four putative GnRH receptors from C. intestinalis. These are the only invertebrate GnRH receptors found to date. Each Ciona GnRH receptor was expressed in COS-7 cells, incubated with each of the six C. intestinalis GnRHs and assayed for a signaling response. GnRH receptors 1, 2, and 3 responded to Ciona GnRH peptides to stimulate intracellular cAMP accumulation. In contrast, only GnRH receptor 1 activated inositol phosphate turnover in response to one of the Ciona GnRHs. The green monkey type II GnRH receptor cDNA was tested as a comparison and a positive control. In conclusion, the four GnRH receptors encoded within the C. intestinalis genome were all transcribed into messenger RNA, but only three of the Ciona GnRH receptors were biologically active in our assays. The Ciona GnRH receptors almost exclusively activated the cAMP pathway.
27
Leppä, S., P. Härkönen y M. Jalkanen. "Steroid-induced epithelial-fibroblastic conversion associated with syndecan suppression in S115 mouse mammary tumor cells." Cell Regulation 2, n.º 1 (enero de 1991): 1–11. http://dx.doi.org/10.1091/mbc.2.1.1.
Texto completoResumen
Cell-matrix interactions play an important role in the maintenance of cell shape, supposed to be mediated by the anchorage of cellular cytoskeleton to extracellular matrix via matrix receptors. In this work the expression of one of the known matrix receptors, syndecan, was studied during the hormone-induced change in the phenotype of Shionogi 115 (S115) mouse mammary tumor cells. In the presence of testosterone, when S115 cells express fibroblastic phenotype, they increased their growth rate and became gradually anchorage independent. These cells, however, revealed strong RGDS-dependent binding to fibronectin (FN) but not binding to the heparin-binding domain of FN. Instead, S115 cells growth without testosterone showed epithelial morphology and binding to the heparin-binding domain of FN, suggesting an alteration of syndecan expression in hormone-treated S115 cells. As quantitated by radioimmunoassay and by Western blot, the amounts of both matrix-binding ectodomain of syndecan and syndecan mRNA (2.6 kb) declined in hormone-treated S115 cells. The addition of antiandrogen cyproterone acetate to culture medium opposed the effect of testosterone on syndecan mRNA. We thus propose that the inactivation of syndecan gene and the consequent suppression of syndecan expression is related to the altered adhesion properties, the disappearance of epithelial phenotype, and, on the other hand, to the appearance of transformed-like phenotype in hormone-treated S115 cells.
28
Sakai, Tsubasa, Tatsuya Yamamoto, Shin Matsubara, Tsuyoshi Kawada y Honoo Satake. "Invertebrate Gonadotropin-Releasing Hormone Receptor Signaling and Its Relevant Biological Actions". International Journal of Molecular Sciences 21, n.º 22 (12 de noviembre de 2020): 8544. http://dx.doi.org/10.3390/ijms21228544.
Texto completoResumen
Gonadotropin-releasing hormones (GnRHs) play pivotal roles in reproduction via the hypothalamus-pituitary-gonad axis (HPG axis) in vertebrates. GnRHs and their receptors (GnRHRs) are also conserved in invertebrates lacking the HPG axis, indicating that invertebrate GnRHs do not serve as “gonadotropin-releasing factors” but, rather, function as neuropeptides that directly regulate target tissues. All vertebrate and urochordate GnRHs comprise 10 amino acids, whereas amphioxus, echinoderm, and protostome GnRH-like peptides are 11- or 12-residue peptides. Intracellular calcium mobilization is the major second messenger for GnRH signaling in cephalochordates, echinoderms, and protostomes, while urochordate GnRHRs also stimulate cAMP production pathways. Moreover, the ligand-specific modulation of signal transduction via heterodimerization between GnRHR paralogs indicates species-specific evolution in Ciona intestinalis. The characterization of authentic or putative invertebrate GnRHRs in various tissues and their in vitro and in vivo activities indicate that invertebrate GnRHs are responsible for the regulation of both reproductive and nonreproductive functions. In this review, we examine our current understanding of and perspectives on the primary sequences, tissue distribution of mRNA expression, signal transduction, and biological functions of invertebrate GnRHs and their receptors.
29
Moore, Graham J. y John M. Matsoukas. "Angiotensin as a model for hormone – receptor interactions". Bioscience Reports 5, n.º 5 (1 de mayo de 1985): 407–16. http://dx.doi.org/10.1007/bf01116558.
Texto completoResumen
Proton magnetic resonance and chemical reactivity studies have demonstrated the presence of a tyrosine charge relay system in angiotensin which is analogous to the serine charge relay system present at the active site of serine proteases. Receptor activation by angiotensin can be explained by electronic effects deriving from an interaction of the charge relay system with stacking of the histidine and phenylalanine rings. Experiments with serine protease inhibitors suggest the possibility that mechanistic features of the interaction of angiotensin with its receptors may apply to other ‘phenoxyl’ hormones including certain peptides, steroids and catecholamines.
30
Nielsen, S., S. Mellemkj˦r, LM Rasmussen, T. Ledet, J. Astrup, J. Weeke y JOL Jørgensen. "Gene transcription of receptors for growth hormone releasing peptides and somatostatin in human pituitary adenomas". Growth Hormone & IGF Research 8, n.º 4 (agosto de 1998): 321. http://dx.doi.org/10.1016/s1096-6374(98)80167-6.
Texto completo
31
Hammerman, M. R. y S. B. Miller. "The growth hormone insulin-like growth factor axis in kidney revisited". American Journal of Physiology-Renal Physiology 265, n.º 1 (1 de julio de 1993): F1—F14. http://dx.doi.org/10.1152/ajprenal.1993.265.1.f1.
Texto completoResumen
Studies characterizing actions of growth hormone (GH) and insulin-like growth factors (IGF) in kidneys of adult and developing animals and humans have provided a good deal of insight into the functions of these peptides. Although certain of the actions may be mediated directly by GH, most appear to result from effects of GH to increase levels of circulating IGF or IGF produced in kidney. In addition to GH, epidermal growth factor (EGF) enhances the renal synthesis of IGF-I. Enhancement of renal IGF-I expression is GH independent in compensatory hypertrophy. Stimulation of kidney IGF-I production also occurs in diabetes mellitus. Renal IGF-I production is elevated in these settings in the absence of changes in circulating IGF-I, consistent with a causative role of renal IGF-I for the accompanying increased glomerular filtration rate and kidney growth. Actions of IGF in kidney are initiated following binding of peptides to specific receptors. Receptor number may be altered during compensatory growth and in diabetes mellitus. In addition to IGF, several IGF binding proteins (IGFBP) are produced in kidney and are likely to both inhibit and enhance the actions of IGF in different circumstances through sequestration of peptides and regulation of peptide interactions with their receptors. Administration of IGF-I to rats following acute ischemic injury hastens the recovery of normal renal function and accelerates the regeneration of the damaged proximal tubular epithelium. IGF-I increases the glomerular filtration rate in humans with normal and reduced functional kidney mass. These findings establish the potential for use of this peptide as a therapeutic agent in the settings of acute and chronic renal failure.
32
Yakovleva, Anastasia A. "Formation of fetal opioid system". Journal of obstetrics and women's diseases 65, n.º 2 (15 de marzo de 2016): 64–69. http://dx.doi.org/10.17816/jowd65264-69.
Texto completoResumen
The article presented literature review about of endogenous opioid system (EOS) formation consist of opioid receptors complex and its ligands (endogenous opioid peptides) in different tissues including placenta. It was shown that formation of fetal EOS is going with anatomic and functional development of the central nervous system and EOS expression begins in the placental tissues as soon as implantation and starts till the end of the pregnancy. Influence of opioid peptides on secretion progesterone, prolactin family peptides, growth hormone, placental lactogens and prolypherine from the trophoblast tissue is discussed.
33
Kim, So Young, Fuming Zhang, Wanghua Gong, Keqiang Chen, Kai Xia, Fei Liu, Richard Gross, Ji Ming Wang, Robert J. Linhardt y Myriam L. Cotten. "Copper regulates the interactions of antimicrobial piscidin peptides from fish mast cells with formyl peptide receptors and heparin". Journal of Biological Chemistry 293, n.º 40 (29 de agosto de 2018): 15381–96. http://dx.doi.org/10.1074/jbc.ra118.001904.
Texto completo
34
Bendena, William G. y Stephen S. Tobe. "Families of allatoregulator sequences: a 2011 perspective1This review is part of a virtual symposium on recent advances in understanding a variety of complex regulatory processes in insect physiology and endocrinology, including development, metabolism, cold hardiness, food intake and digestion, and diuresis, through the use of omics technologies in the postgenomic era." Canadian Journal of Zoology 90, n.º 4 (abril de 2012): 521–44. http://dx.doi.org/10.1139/z2012-012.
Texto completoResumen
Three different peptide families have been named “allatostatins” (ASTs), based on their initial purifications which were based on their ability to inhibit juvenile hormone (JH) biosynthesis. These include (i) a family of peptides that have a consensus C-terminal sequence Y/FXFGL-NH2; (ii) a family of peptides with a conserved C-terminal sequence W(X)6W-NH2; and(iii) a family of peptides with C-terminal sequence PISCF, some of which are C-terminally-amidated. Each allatostatin family has functions distinct and apart from the inhibition of JH biosynthesis. A peptide family known as the “allatotropins” serve to stimulate JH biosynthesis. This family of peptides also has been proven to exert multiple effects dependent on the species in question. Genome and peptidome projects are uncovering new members of these families and it is clear that these structures are not just confined to Insecta but are found in a range of invertebrates. The receptors for these neuropeptides have been identified and tested experimentally for specific ligand binding. The Y/FXFGLa-ASTs exert their action through galanin-like receptors, W(X)6Wa-ASTs through a sex peptide-binding receptor, and PISCF-ASTs through somatostatin-like receptors. These receptors are conserved through evolutionary time and are being identified in numerous invertebrates by way of genome projects.
35
Lightman, S. L. "The neuroendocrine paraventricular hypothalamus: receptors, signal transduction, mRNA and neurosecretion". Journal of Experimental Biology 139, n.º 1 (1 de septiembre de 1988): 31–49. http://dx.doi.org/10.1242/jeb.139.1.31.
Texto completoResumen
The hypothalamus is one of the most studied areas of the central nervous system. Many of its functions are understood and there is an extensive literature on its role in the control of pituitary hormone secretion, autonomic nervous system activity, regulation of salt, water and food ingestion, body temperature regulation and aspects of behaviour. Although the role of the hypothalamus in the control of pituitary secretion was postulated in the early 1900s, the chemical nature of these control mechanisms has only been documented in the last few years. The opioid peptides represent one particular family of chemical compounds which have been shown to have many effects on pituitary hormone secretion. Exogenous opioids inhibit the neurosecretion of both vasopressin and oxytocin from the posterior pituitary neurosecretory terminals of hypothalamic cell bodies. Opioids also have major actions on the secretory activity of the anterior pituitary which has no innervation from the hypothalamus, but which is regulated by blood-borne factors in the hypophyseal portal circulation which runs from the median eminence of the hypothalamus. It was therefore of considerable interest when it was discovered that endogenous opioid peptides could be detected both in the neurohypophyseal system and in cells which project into the median eminence. The simple presence of a peptide in a neurone does not necessarily imply a function. If, however, we can demonstrate that regulation of the synthesis of the peptide occurs in a manner which corresponds with the expected role of the agent, this provides powerful data in support of a genuine physiological function. The elucidation of the genomic structure of the precursors for the three endogenous opioid peptides has provided us with the ability to measure mRNA for these peptides in defined areas of the brain and to assess their response to appropriate stimuli. Not only does mRNA for the endogenous opioid dynorphin coexist in the same cells as vasopressin but we have now been able to demonstrate that stimuli to vasopressin secretion also result in a markedly increased accumulation of dynorphin mRNA. Similarly, previous studies have shown that opioid peptides derived from another precursor--pro-enkephalin A--coexist with corticotrophin releasing factor in a different group of hypothalamic cells. We have now been able to demonstrate that stresses which result in an accumulation of corticotrophin releasing factor mRNA also result in increased pro-enkephalin mRNA in the same area. This considerably strengthens the hypothesis that endogenous opioids do play a significant role in the control of hypophyseal secretion.(ABSTRACT TRUNCATED AT 400 WORDS)
36
Samson, Willis K., Blake D. Alexander, Karl D. Skala, F. L. Steven Huang y R. Jerrold Fulton. "Central peptidergic mechanisms controlling reproductive hormone secretion: Novel methodology reveals a role for the natriuretic peptides". Canadian Journal of Physiology and Pharmacology 70, n.º 5 (1 de mayo de 1992): 773–78. http://dx.doi.org/10.1139/y92-102.
Texto completoResumen
A variety of neural factors can influence reproductive hormone secretion by neuromodulatory actions within the hypothalamus or neuroendocrine actions within the anterior pituitary gland. Passive immunoneutralization and antagonist administration protocols have suggested physiological roles for a number of these factors; however, both experimental approaches have severe technical limitations. We have developed novel methodology utilizing cytotoxin cell targeting with neuropeptides linked to the toxic A chain of the plant cytotoxin ricin. With this methodology we can target and destroy in vivo or in vitro cells bearing receptors for that peptide. Ricin A chain conjugated to atrial natriuretic peptide (ANP), a neuropeptide known to pharmacologically inhibit luteinizing hormone-releasing hormone (LHRH) release, was injected into the cerebroventricular system of intact, cycling rats and ovariectomized rats. Cytotoxin conjugate treatment significantly lengthened the estrous cycle. In ovariectomized rats the luteinizing hormone surge induced by steroid priming was completely inhibited. LHRH content of the median eminences of these rats was not significantly altered. These data suggest that ANP binding to clearance receptors in the hypothalamus displaces the C-type natriuretic peptide (CNP) from the shared clearance receptor, making more CNP available to inhibit LHRH release. In the absence of cells bearing the clearance receptor all available CNP binds to the ANPR-B receptor and exerts its effect via an inhibitory interneuron, since LHRH fibers are spared by this treatment.Key words: atrial peptides, hypothalamus, reproduction, cytotoxin, gonadotropins.
37
Lyson, Krzysztof, Giuliana Ceriani, Akira Takashima, Anna Catania y James M. Lipton. "Binding of Anti-Inflammatoryα-Melanocyte-Stimulating-Hormone Peptides and Proinflammatory Cytokines to Receptors on Melanoma Cells". Neuroimmunomodulation 1, n.º 2 (1994): 121–26. http://dx.doi.org/10.1159/000097145.
Texto completo
38
Foord, S. M., S. Jupe y J. Holbrook. "Bioinformatics and type II G-protein-coupled receptors". Biochemical Society Transactions 30, n.º 4 (1 de agosto de 2002): 473–79. http://dx.doi.org/10.1042/bst0300473.
Texto completoResumen
The best known family B, or Type II, G-protein-coupled receptors (GPCRs) recognize peptides as ligands. The receptors for corticotrophin-releasing factor, parathyroid hormone and secretin typify this group. However, there are only 15 such GPCRs. Many other receptors share sequence homology and have been assigned to this family. The ten ‘Frizzled’ and one ‘Smoothened’ receptors show the lowest sequence homology and are not necessarily G-protein coupled. Drosophila genetics have enabled our understanding of their biology. In contrast, relatively little is known about the largest group with family B, the 33 ‘large amino termini’ or large N-terminal family B seven-transmembrane (LNB 7TM) receptors. This review highlights the similarities found between family B receptors and provides a classification of LNB 7TM receptors.
39
Li, Hongliang, Taylor Murphy, Ling Zhang, Bing Huang, Vineet Veitla, Benjamin J. Scherlag, David C. Kem y Xichun Yu. "β1-Adrenergic and M2 Muscarinic Autoantibodies and Thyroid Hormone Facilitate Induction of Atrial Fibrillation in Male Rabbits". Endocrinology 157, n.º 1 (1 de enero de 2016): 16–22. http://dx.doi.org/10.1210/en.2015-1655.
Texto completoResumen
Abstract Activating autoantibodies to the β1-adrenergic and M2 muscarinic receptors are present in a very high percentage of patients with Graves' disease and atrial fibrillation (AF). The objective of this study was to develop a reproducible animal model and thereby to examine the impact of these endocrine-like autoantibodies alone and with thyroid hormone on induction of thyroid-associated atrial tachyarrhythmias. Five New Zealand white rabbits were coimmunized with peptides from the second extracellular loops of the β1-adrenergic and M2 muscarinic receptors to produce both sympathomimetic and parasympathomimetic antibodies. A catheter-based electrophysiological study was performed on anesthetized rabbits before and after immunization and subsequent treatment with thyroid hormone. Antibody expression facilitated the induction of sustained sinus, junctional and atrial tachycardias, but not AF. Addition of excessive thyroid hormone resulted in induced sustained AF in all animals. AF induction was blocked acutely by the neutralization of these antibodies with immunogenic peptides despite continued hyperthyroidism. The measured atrial effective refractory period as one parameter of AF propensity shortened significantly after immunization and was acutely reversed by peptide neutralization. No further decrease in the effective refractory period was observed after the addition of thyroid hormone, suggesting other cardiac effects of thyroid hormone may contribute to its role in AF induction. This study demonstrates autonomic autoantibodies and thyroid hormone potentiate the vulnerability of the heart to AF, which can be reversed by decoy peptide therapy. These data help fulfill Witebsky's postulates for an increased autoimmune/endocrine basis for Graves' hyperthyroidism and AF.
40
Anderson, Erica J. P., Isin Çakir, Sheridan J. Carrington, Roger D. Cone, Masoud Ghamari-Langroudi, Taneisha Gillyard, Luis E. Gimenez y Michael J. Litt. "60 YEARS OF POMC: Regulation of feeding and energy homeostasis by α-MSH". Journal of Molecular Endocrinology 56, n.º 4 (mayo de 2016): T157—T174. http://dx.doi.org/10.1530/jme-16-0014.
Texto completoResumen
The melanocortin peptides derived from pro-opiomelanocortin (POMC) were originally understood in terms of the biological actions of α-melanocyte-stimulating hormone (α-MSH) on pigmentation and adrenocorticotrophic hormone on adrenocortical glucocorticoid production. However, the discovery of POMC mRNA and melanocortin peptides in the CNS generated activities directed at understanding the direct biological actions of melanocortins in the brain. Ultimately, discovery of unique melanocortin receptors expressed in the CNS, the melanocortin-3 (MC3R) and melanocortin-4 (MC4R) receptors, led to the development of pharmacological tools and genetic models leading to the demonstration that the central melanocortin system plays a critical role in the regulation of energy homeostasis. Indeed, mutations in MC4R are now known to be the most common cause of early onset syndromic obesity, accounting for 2–5% of all cases. This review discusses the history of these discoveries, as well as the latest work attempting to understand the molecular and cellular basis of regulation of feeding and energy homeostasis by the predominant melanocortin peptide in the CNS, α-MSH.
41
Abdennebi, L., L. Couture, D. Grebert, E. Pajot, R. Salesse y JJ Remy. "Generating FSH antagonists and agonists through immunization against FSH receptor N-terminal decapeptides". Journal of Molecular Endocrinology 22, n.º 2 (1 de abril de 1999): 151–59. http://dx.doi.org/10.1677/jme.0.0220151.
Texto completoResumen
Follicle-stimulating hormone (FSH) via interaction with G-protein coupled specific receptors plays a central role in the control of gametogenesis in mammals of both sexes. In females, FSH is crucial for follicle growth, follicle maturation and ovulation. FSH receptors, together with luteinizing hormone-chorionic gonadotropin and thyrotropin receptors belong to a subfamily of structurally related receptors within the seven transmembrane receptor family. Among several other regions, the N-terminus of these receptors is believed to be responsible for important specific hormone-receptor contact sites. Recombinant filamentous phages displaying at their surface three overlapping N-terminal decapeptides of the FSH receptor, peptides A18-27, B25-34 and C29-38 were constructed. Ewes and female mice were immunized against the three FSH receptor (FSHR) recombinant phages. Immunoglobulins purified from immunized animals were analyzed for their biochemical properties on a Chinese hamster ovary cell line expressing the porcine FSH receptor. AntiA and antiB immunoglobulins (IgGs) behave as antagonists for 125I-FSH binding and for FSH-dependent cAMP production, while antiC IgGs did not compete for hormone binding. By contrast, antibodies against the C29-38 peptide displayed FSH agonist activity and stimulated the FSH receptor, whereas antiA and antiB IgGs did not. Furthermore, when the FSHR phages were used as peptidic vaccines, they induced a reversible inhibition of ovulation rate in ewes, and impaired fertility in female mice.
42
Coskun, Tamer, Libbey S. O’Farrell, Samreen K. Syed, Daniel A. Briere, Lisa S. Beavers, Susan L. DuBois, Mervyn D. Michael, Jeffry B. Franciskovich, David G. Barrett y Alexander M. Efanov. "Activation of Prostaglandin E Receptor 4 Triggers Secretion of Gut Hormone Peptides GLP-1, GLP-2, and PYY". Endocrinology 154, n.º 1 (1 de enero de 2013): 45–53. http://dx.doi.org/10.1210/en.2012-1446.
Texto completoResumen
Prostaglandins E1 and E2 are synthesized in the intestine and mediate a range of gastrointestinal functions via activation of the prostanoid E type (EP) family of receptors. We examined the potential role of EP receptors in the regulation of gut hormone secretion from L cells. Analysis of mRNA expression in mouse enteroendocrine GLUTag cells demonstrated the abundant expression of EP4 receptor, whereas expression of other EP receptors was much lower. Prostaglandin E1 and E2, nonselective agonists for all EP receptor subtypes, triggered glucagon like peptide 1 (GLP-1) secretion from GLUTag cells, as did the EP4-selective agonists CAY10580 and TCS2510. The effect of EP4 agonists on GLP-1 secretion was blocked by incubation of cells with the EP4-selective antagonist L161,982 or by down-regulating EP4 expression with specific small interfering RNA. Regulation of gut hormone secretion with EP4 agonists was further studied in mice. Administration of EP4 agonists to mice produced a significant elevation of plasma levels of GLP-1, glucagon like peptide 2 (GLP-2) and peptide YY (PYY), whereas gastric inhibitory peptide (GIP) levels were not increased. Thus, our data demonstrate that activation of the EP4 receptor in enteroendocrine L cells triggers secretion of gut hormones.
43
Clemetson, Kenneth J., Jeannine M. Clemetson, Amanda E. I. Proudfoot, Christine A. Power, Marco Baggiolini y Timothy N. C. Wells. "Functional expression of CCR1, CCR3, CCR4, and CXCR4 chemokine receptors on human platelets". Blood 96, n.º 13 (15 de diciembre de 2000): 4046–54. http://dx.doi.org/10.1182/blood.v96.13.4046.
Texto completoResumen
Abstract Platelets are known to contain platelet factor 4 and β-thromboglobulin, α-chemokines containing the CXC motif, but recent studies extended the range to the β-family characterized by the CC motif, including RANTES and Gro-α. There is also evidence for expression of chemokine receptors CCR4 and CXCR4 in platelets. This study shows that platelets have functional CCR1, CCR3, CCR4, and CXCR4 chemokine receptors. Polymerase chain reaction detected chemokine receptor messenger RNA in platelet RNA. CCR1, CCR3, and especially CCR4 gave strong signals; CXCR1 and CXCR4 were weakly positive. Flow cytometry with specific antibodies showed the presence of a clear signal for CXCR4 and weak signals for CCR1 and CCR3, whereas CXCR1, CXCR2, CXCR3, and CCR5 were all negative. Immunoprecipitation and Western blotting with polyclonal antibodies to cytoplasmic peptides clearly showed the presence of CCR1 and CCR4 in platelets in amounts comparable to monocytes and CCR4 transfected cells, respectively. Chemokines specific for these receptors, including monocyte chemotactic protein 1, macrophage inflammatory peptide 1α, eotaxin, RANTES, TARC, macrophage-derived chemokine, and stromal cell–derived factor 1, activate platelets to give Ca++ signals, aggregation, and release of granule contents. Platelet aggregation was dependent on release of adenosine diphosphate (ADP) and its interaction with platelet ADP receptors. Part, but not all, of the Ca++ signal was due to ADP release feeding back to its receptors. Platelet activation also involved heparan or chondroitin sulfate associated with the platelet surface and was inhibited by cleavage of these glycosaminoglycans or by heparin or low molecular weight heparin. These platelet receptors may be involved in inflammatory or allergic responses or in platelet activation in human immunodeficiency virus infection.
44
Clemetson, Kenneth J., Jeannine M. Clemetson, Amanda E. I. Proudfoot, Christine A. Power, Marco Baggiolini y Timothy N. C. Wells. "Functional expression of CCR1, CCR3, CCR4, and CXCR4 chemokine receptors on human platelets". Blood 96, n.º 13 (15 de diciembre de 2000): 4046–54. http://dx.doi.org/10.1182/blood.v96.13.4046.h8004046_4046_4054.
Texto completoResumen
Platelets are known to contain platelet factor 4 and β-thromboglobulin, α-chemokines containing the CXC motif, but recent studies extended the range to the β-family characterized by the CC motif, including RANTES and Gro-α. There is also evidence for expression of chemokine receptors CCR4 and CXCR4 in platelets. This study shows that platelets have functional CCR1, CCR3, CCR4, and CXCR4 chemokine receptors. Polymerase chain reaction detected chemokine receptor messenger RNA in platelet RNA. CCR1, CCR3, and especially CCR4 gave strong signals; CXCR1 and CXCR4 were weakly positive. Flow cytometry with specific antibodies showed the presence of a clear signal for CXCR4 and weak signals for CCR1 and CCR3, whereas CXCR1, CXCR2, CXCR3, and CCR5 were all negative. Immunoprecipitation and Western blotting with polyclonal antibodies to cytoplasmic peptides clearly showed the presence of CCR1 and CCR4 in platelets in amounts comparable to monocytes and CCR4 transfected cells, respectively. Chemokines specific for these receptors, including monocyte chemotactic protein 1, macrophage inflammatory peptide 1α, eotaxin, RANTES, TARC, macrophage-derived chemokine, and stromal cell–derived factor 1, activate platelets to give Ca++ signals, aggregation, and release of granule contents. Platelet aggregation was dependent on release of adenosine diphosphate (ADP) and its interaction with platelet ADP receptors. Part, but not all, of the Ca++ signal was due to ADP release feeding back to its receptors. Platelet activation also involved heparan or chondroitin sulfate associated with the platelet surface and was inhibited by cleavage of these glycosaminoglycans or by heparin or low molecular weight heparin. These platelet receptors may be involved in inflammatory or allergic responses or in platelet activation in human immunodeficiency virus infection.
45
Schiöth, Helgi B., Philip Yook, Ruta Muceniece, Jarl E. S. Wikberg y Michael Szardenings. "Chimeric Melanocortin MC1 and MC3 Receptors: Identification of Domains Participating in Binding of Melanocyte-Stimulating Hormone Peptides". Molecular Pharmacology 54, n.º 1 (1 de julio de 1998): 154–61. http://dx.doi.org/10.1124/mol.54.1.154.
Texto completo
46
Córdoba-Chacón, Jose, Manuel D. Gahete, Justo P. Castaño, Rhonda D. Kineman y Raul M. Luque. "Homologous and Heterologous in Vitro Regulation of Pituitary Receptors for Somatostatin, Growth Hormone (GH)-Releasing Hormone, and Ghrelin in a Nonhuman Primate (Papio anubis)". Endocrinology 153, n.º 1 (1 de enero de 2012): 264–72. http://dx.doi.org/10.1210/en.2011-1677.
Texto completoResumen
Secretion of GH by pituitary somatotrophs is primarily stimulated by GHRH and ghrelin and inhibited by somatostatin through the activation of specific receptors [GHRH receptor (GHRH-R), GH secretagogue receptor (GHS-R) and somatostatin receptors (sst1–5), respectively]. However, we have shown that somatostatin, at low doses, can also stimulate GH release, directly and specifically, in primary pituitary cultures from a nonhuman primate (baboons, Papio anubis) and pigs. To determine whether somatostatin, GHRH, and ghrelin can also regulate the expression of their receptors in primates, pituitary cultures from baboons were treated for 4 h with GHRH or ghrelin (10−8m) or with high (10−7m) and low (10−15m) doses of somatostatin, and GH release and expression levels of all receptors were measured. GHRH/ghrelin decreased the expression of their respective receptors (GHRH-R and GHS-R). Both peptides increased sst1, only GHRH decreased sst5 expression, whereas sst2 expression remained unchanged. The effects of GHRH/ghrelin were completely mimicked by forskolin (adenylate cyclase activator) and phorbol 12-myristate 13-acetate (protein kinase C activator), respectively, indicating the regulation of receptor subtype levels by GHRH and ghrelin involved distinct signaling pathways. In contrast, high-dose somatostatin did not alter GH release but increased sst1, sst2, and sst5 expression, whereas GHRH-R and GHS-R expression were unaffected. Interestingly, low-dose somatostatin increased GH release and sst1 mRNA but decreased sst5 and GHRH-R expression, similar to that observed for GHRH. Altogether, our data show for the first time in a primate model that the primary regulators of somatotroph function (GHRH/ghrelin/somatostatin) exert both homologous and heterologous regulation of receptor synthesis which is dose and subtype dependent and involves distinct signaling pathways.
47
Taylor, Meghan M., Sara L. Bagley y Willis K. Samson. "Intermedin/Adrenomedullin-2 Inhibits Growth Hormone Release from Cultured, Primary Anterior Pituitary Cells". Endocrinology 147, n.º 2 (1 de febrero de 2006): 859–64. http://dx.doi.org/10.1210/en.2005-0949.
Texto completoResumen
Intermedin (IMD), a novel member of the adrenomedullin (AM), calcitonin gene-related peptide (CGRP), amylin (AMY) peptide family, has been reported to act promiscuously at all the known receptors for these peptides. Like AM and CGRP, IMD acts in the circulation to decrease blood pressure and in the brain to inhibit food intake, effects that could be explained by activation of the known CGRP, AM, or AMY receptors. Because AM, CGRP, and AMY have been reported to affect hormone secretion from the anterior pituitary gland, we examined the effects of IMD on GH, ACTH, and prolactin secretion from dispersed anterior pituitary cells harvested from adult male rats. IMD, in log molar concentrations ranging from 1.0 pm to 100 nm, failed to significantly alter basal release of the three hormones. Similarly, IMD failed to significantly alter CRH-stimulated ACTH or TRH-stimulated prolactin secretion in vitro. However, IMD concentration-dependently inhibited GHRH-stimulated GH release from these cell cultures. The effects of IMD, although requiring higher concentrations, were as efficacious as those of somatostatin and, like somatostatin, may be mediated, at least in part, by decreasing cAMP accumulation. These actions of IMD were not shared by other members of the AM-CGRP-AMY family of peptides, suggesting the presence of a novel, unique IMD receptor in the anterior pituitary gland and a potential neuroendocrine action of IMD to interact with the hypothalamic mechanisms controlling growth and metabolism.
48
Gensure, Robert C., Bhaskar Ponugoti, Yasemin Gunes, Madhusudhan R. Papasani, Beate Lanske, Murat Bastepe, David A. Rubin y Harald Jüppner. "Identification and Characterization of Two Parathyroid Hormone-Like Molecules in Zebrafish". Endocrinology 145, n.º 4 (1 de abril de 2004): 1634–39. http://dx.doi.org/10.1210/en.2003-0964.
Texto completoResumen
Abstract Zebrafish (Danio rerio) have receptors homologous to the human PTH (hPTH)/PTHrP receptor (PTH1R) and PTH-2 receptor (PTH2R) and an additional receptor (PTH3R) with high homology to the PTH1R. To find natural ligands for zPTH1R and zPTH3R, we searched the zebrafish genomic database and discovered two distinct regions that, when translated (zPTH1 and zPTH2), showed high homology to hPTH. Isolation of cDNAs and determination of the intron/exon boundaries revealed genomic structures which were similar to known PTHs. Peptides consisting of the first 34 amino acids after the pre- and prosequences of the zebrafish PTHs (zPTHs) were synthesized and were shown to be fully active at the hPTH1R. zPTH2(1–34) was, however, approximately 30-fold less potent at the zPTH1R than hPTH(1–34), hPTHrP(1–36), and zPTH1(1–34). When tested with zPTH3R, zPTH1(1–34) and hPTHrP(1–36) showed similar potencies, whereas the potency of zPTH2(1–34) was moderately (3-fold) reduced. To determine whether other fishes have multiple PTHs, we searched the genomic database of the Japanese pufferfish (Takifugu rubripes) and identified zPTH1 and zPTH2 homologs. Phylogenetic analysis showed that PTHs from zebrafish and pufferfish are more closely related to each other than to known mammalian PTH homologs or to PTHrP and tuberoinfundibular peptide of 39 residues. This is consistent with evolution of two teleost PTH-like peptides occurring after the evolutionary divergence between fishes and mammals. Overall, the PTH system appears more complex in fishes than in mammals, providing evidence of continued evolution in nontetrapod species. The availability of multiple forms of fish PTH and their receptors provide additional tools for PTH ligand/receptor structure-function studies.
49
Getting, S. J., M. Kaneva, Y. Bhadresa, D. Renshaw, Giovanna Leoni, H. B. Patel, M. J. P. Kerrigan y I. C. Locke. "Melanocortin Peptide Therapy for the Treatment of Arthritic Pathologies". Scientific World JOURNAL 9 (2009): 1394–414. http://dx.doi.org/10.1100/tsw.2009.163.
Texto completoResumen
Arthritic pathologies are a major cause of morbidity within the western world, with rheumatoid arthritis affecting approximately 1% of adults. This review highlights the therapeutic potential of naturally occurring hormones and their peptides, in both arthritic models of disease and patients. The arthritides represent a group of closely related pathologies in which cytokines, joint destruction, and leukocytes play a causal role. Here we discuss the role of naturally occurring pro-opiomelanocortin (POMC)-derived melanocortin peptides (e.g., alpha melanocyte stimulating hormone [a-MSH]) and synthetic derivatives in these diseases. Melanocortins exhibit their biological efficacy by modulating proinflammatory cytokines and subsequent leukocyte extravasation. Their biological effects are mediated via seven transmembrane G-protein-coupled receptors, of which five have been cloned, identified, and termed MC1to MC5. Adrenocorticotrophic hormone represents the parent molecule of the melanocortins; the first 13 amino acids of which (termed a-MSH) have been shown to be the most pharmacologically active region of the parent hormone. The melanocortin peptides have been shown to display potent anti-inflammatory effects in both animal models of disease and patients. The potential anti-inflammatory role for endogenous peptides in arthritic pathologies is in its infancy. The ability to inhibit leukocyte migration, release of cytokines, and induction of anti-inflammatory proteins appears to play an important role in affording protection in arthritic injury, and thus may lead to potential therapeutic targets.
50
Pati, Debananda y Hamid R. Habibi. "Characterization of gonadotropin-releasing hormone (GnRH) receptors in the ovary of common carp (Cyprinus carpio)". Canadian Journal of Physiology and Pharmacology 70, n.º 2 (1 de febrero de 1992): 268–74. http://dx.doi.org/10.1139/y92-033.
Texto completoResumen
Gonadotropin-releasing hormone (GnRH) binding sites have been characterized in the fully mature common carp ovary, using an analog of salmon GnRH ([D-Arg6,Trp7,Leu8,Pro9-NEt]-GnRH; sGnRH-A) as a labeled ligand. Binding of sGnRH-A to carp follicular membrane preparation was found to be time-, temperature-, and pH-dependent. Optimal binding was achieved after 40 min of incubation at 4 °C at pH 7.6; binding was found to be unstable at room temperature. Binding of radioligand was a function of tissue concentration, with a linear correlation over the range of 8.0–40.0 μg membrane protein per tube. Incubation of membrane preparations with increasing levels of [125I]sGnRH-A revealed saturable binding at radioligand concentrations greater than 400 nM. The binding of [125I]sGnRH-A to the carp ovary was also found to be reversible; addition of unlabeled sGnRH-A (10−6 M) after reaching equilibrium resulted in complete dissociation of [125I]sGnRH-A within 30 min, and the log dissociation plot indicated the existence of a single class of binding sites. Addition of unlabeled sGnRH-A displaced the bound [125I]sGnRH-A in a dose-related manner. Hill plot as well as Scatchard analysis suggested the presence of one class of high affinity GnRH binding sites. Bound [125I]sGnRH-A was also found to be displaceable by other GnRH peptides, including sGnRH ([Trp7,Leu8]-GnRH), cGnRH-II ([His5,Trp7,Tyr8]-GnRH) and a GnRH antagonist ([D-pGlu1,D-Phe2,D-Trp3,6]-GnRH; GnRH-ANT) in a parallel fashion, indicating that these peptides bind to the same class of binding sites. sGnRH-A and cGnRH-II were found to bind with greater affinities than sGnRH and GnRH-ANT to the carp ovarian binding sites. These results provide for the first time characterization of GnRH binding sites in the ovary of a teleost species, Cyprinus carpio.Key words: gonadotropin-releasing hormone, luteinizing hormone releasing hormone, receptor, ovary, carp, Cyprinus carpio.