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Journal articles on the topic 'Orexin 1 receptor'

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Published: 11 March 2023

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1

Banerjee, Indrajit. "Orexin Receptor Competitive Antagonists: A Novel target of the Sedative and hypnotics drugs for the pharmacotherapy of Insomnia." Nepal Journal of Epidemiology 8, no. 1 (2018): 713–15. http://dx.doi.org/10.3126/nje.v8i1.21139.

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Orexins are peptide neurotransmitters which are produced in the lateral and posterior part of the hypothalamus in the brain. There are two Orexin receptors which has been identified till date viz. Orexin 1 (OX 1) and Orexin 2 (OX 2 receptor).
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2

Jöhren, Olaf, Norbert Brüggemann, Andreas Dendorfer, and Peter Dominiak. "Gonadal Steroids Differentially Regulate the Messenger Ribonucleic Acid Expression of Pituitary Orexin Type 1 Receptors and Adrenal Orexin Type 2 Receptors." Endocrinology 144, no. 4 (2003): 1219–25. http://dx.doi.org/10.1210/en.2002-0030.

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Abstract Hypothalamic prepro-orexin as well as pituitary and adrenal orexin receptors are gender-specifically expressed. To assess the regulation by gonadal steroids, we investigated the effect of 17β-estradiol in female and of testosterone in male rats on prepro-orexin and orexin receptor mRNA expression. Rats were either sham-operated or gonadectomized and subsequently treated with placebo, 17β-estradiol, or testosterone for 21 d. Tissue mRNA levels of prepro-orexin, orexin type-1 (OX1), and orexin type-2 (OX2) receptors were measured using quantitative real-time RT-PCR. In female rats, pitu
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3

Patel, Vanlata H., Emmanouil Karteris, Jing Chen, et al. "Functional cardiac orexin receptors: role of orexin-B/orexin 2 receptor in myocardial protection." Clinical Science 132, no. 24 (2018): 2547–64. http://dx.doi.org/10.1042/cs20180150.

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Orexins/hypocretins exert cardiovascular effects which are centrally mediated. In the present study, we tested whether orexins and their receptors may also act in an autocrine/paracrine manner in the heart exerting direct effects. Quantitative reverse transcription-PCR (RT-PCR), immunohistochemical and Western blot analyses revealed that the rat heart expresses orexins and orexin receptors (OXR). In isolated rat cardiomyocytes, only orexin-B (OR-B) caused an increase in contractile shortening, independent of diastolic or systolic calcium levels. A specific orexin receptor-2 (OX2R) agonist ([Al
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4

López, M., R. Señaris, R. Gallego, et al. "Orexin Receptors Are Expressed in the Adrenal Medulla of the Rat." Endocrinology 140, no. 12 (1999): 5991–94. http://dx.doi.org/10.1210/endo.140.12.7287.

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Abstract Two recently discovered hypothalamic peptides, orexin-A and orexin-B, play a role as mediators in the central mechanisms that regulate feeding behavior and sleep control. These peptides bind and activate two orexin receptors that belong to the G-protein coupled receptor superfamily. Morphological studies have detected mRNA expression of orexin receptors exclusively in the rat central nervous system. In this paper we demonstrate a strong level of expression of orexin receptor 1 and 2 in the adrenal medulla of the rat by RT-PCR immunohistochemistry. The results of the present study prov
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Digby, J. E., J. Chen, J. Y. Tang, H. Lehnert, R. N. Matthews, and H. S. Randeva. "Orexin receptor expression in human adipose tissue: effects of orexin-A and orexin-B." Journal of Endocrinology 191, no. 1 (2006): 129–36. http://dx.doi.org/10.1677/joe.1.06886.

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Orexin-A and orexin-B, via their receptors orexin-1 receptor (OX1R) and orexin-2 receptor (OX2R) have been shown to play a role in the regulation of feeding, body weight, and energy expenditure. Adipose tissue also contributes significantly to the maintenance of body weight by interacting with a complex array of bioactive peptides; however, there are no data as yet on the expression of orexin components in adipose tissue. We, therefore, analyzed the expression of OX1R and OX2R in human adipose tissue and determined functional responses to orexin-A and orexin-B. OX1R and OX2R mRNA expression wa
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6

Katzman, Martin A., and Matthew P. Katzman. "Neurobiology of the Orexin System and Its Potential Role in the Regulation of Hedonic Tone." Brain Sciences 12, no. 2 (2022): 150. http://dx.doi.org/10.3390/brainsci12020150.

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Orexin peptides comprise two neuropeptides, orexin A and orexin B, that bind two G-protein coupled receptors (GPCRs), orexin receptor 1 (OXR1) and orexin receptor 2 (OXR2). Although cell bodies that produce orexin peptides are localized in a small area comprising the lateral hypothalamus and adjacent regions, orexin-containing fibres project throughout the neuraxis. Although orexins were initially described as peptides that regulate feeding behaviour, research has shown that orexins are involved in diverse functions that range from the modulation of autonomic functions to higher cognitive func
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7

Barreiro, M. L., R. Pineda, V. M. Navarro, et al. "Orexin 1 Receptor Messenger Ribonucleic Acid Expression and Stimulation of Testosterone Secretion by Orexin-A in Rat Testis." Endocrinology 145, no. 5 (2004): 2297–306. http://dx.doi.org/10.1210/en.2003-1405.

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Abstract Orexins are hypothalamic neuropeptides primarily involved in the regulation of food intake and arousal states. In addition, a role for orexins as central neuroendocrine modulators of reproductive function has recently emerged. Prepro-orexin and orexin type-1 receptor mRNAs have been detected in the rat testis. This raises the possibility of additional peripheral actions of orexins in the control of reproductive axis, which remains so far unexplored. To analyze the biological effects and mechanisms of action of orexins in the male gonad, we evaluated testicular expression of orexin rec
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8

Shirasaka, Tetsuro, Satoshi Miyahara, Takato Kunitake, et al. "Orexin depolarizes rat hypothalamic paraventricular nucleus neurons." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 281, no. 4 (2001): R1114—R1118. http://dx.doi.org/10.1152/ajpregu.2001.281.4.r1114.

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Orexins, also called hypocretins, are newly discovered hypothalamic peptides that are thought to be involved in various physiological functions. In spite of the fact that orexin receptors, especially orexin receptor 2, are abundant in the hypothalamic paraventricular nucleus (PVN), the effects of orexins on PVN neurons remain unknown. Using a whole cell patch-clamp recording technique, we investigated the effects of orexin-B on PVN neurons of rat brain slices. Bath application of orexin-B (0.01–1.0 μM) depolarized 80.8% of type 1 ( n = 26) and 79.2% of type 2 neurons tested ( n = 24) in the PV
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9

Chen, Jing, and Harpal S. Randeva. "Genomic Organization of Mouse Orexin Receptors: Characterization of Two Novel Tissue-Specific Splice Variants." Molecular Endocrinology 18, no. 11 (2004): 2790–804. http://dx.doi.org/10.1210/me.2004-0167.

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Abstract In humans and rat, orexins orchestrate divergent actions through their G protein-coupled receptors, orexin-1 (OX1R) and orexin-2 (OX2R). Orexins also play an important physiological role in mouse, but the receptors through which they function are not characterized. To characterize the physiological role(s) of orexins in the mouse, we cloned and characterized the mouse orexin receptor(s), mOX1R and mOX2R, using rapid amplification of cDNA (mouse brain) ends, RT-PCR, and gene structure analysis. The mOX1R cDNA encodes a 416-amino acid (aa) receptor. We have identified two alternative C
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10

Bruns, Ingmar, Patrick Cadeddu, Sebastian Büst, et al. "The Neuropeptides Orexin a and B Have An Impact on Functional Properties of Human CD34+ Stem and Progenitor Cells." Blood 112, no. 11 (2008): 1393. http://dx.doi.org/10.1182/blood.v112.11.1393.1393.

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Abstract Orexin receptors play a role in regulation of sleep-wake-rhythm, food intake and energy homeostasis and they were long thought to be exclusively expressed in the nervous system. During the last years orexin receptors are being identified in a growing number of peripheral tissues. We have earlier detected orexin receptor 1 and 2 expression on human CD34+ blood stem and progenitor cells. Still, the sources of their physiological ligands, the peptides orexin A and B, seem to be restricted to the central nerve system to this date. The main downstream signaling pathways of the orexin recep
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11

Lang, Manja, Richard M. Söll, Franz Dürrenberger, Frank M. Dautzenberg, and Annette G. Beck-Sickinger. "Structure−Activity Studies of Orexin A and Orexin B at the Human Orexin 1 and Orexin 2 Receptors Led to Orexin 2 Receptor Selective and Orexin 1 Receptor Preferring Ligands." Journal of Medicinal Chemistry 47, no. 5 (2004): 1153–60. http://dx.doi.org/10.1021/jm030982t.

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12

Karteris, Emmanouil, Rachel J. Machado, Jing Chen, Sevasti Zervou, Edward W. Hillhouse, and Harpal S. Randeva. "Food deprivation differentially modulates orexin receptor expression and signaling in rat hypothalamus and adrenal cortex." American Journal of Physiology-Endocrinology and Metabolism 288, no. 6 (2005): E1089—E1100. http://dx.doi.org/10.1152/ajpendo.00351.2004.

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Although starvation-induced biochemical and metabolic changes are perceived by the hypothalamus, the adrenal gland plays a key role in the integration of metabolic activity and energy balance, implicating feeding as a major synchronizer of rhythms in the hypothalamic-pituitary-adrenal (HPA) axis. Given that orexins are involved in regulating food intake and activating the HPA axis, we hypothesized that food deprivation, an acute challenge to the systems that regulate energy balance, should elicit changes in orexin receptor signaling at the hypothalamic and adrenal levels. Food deprivation indu
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13

Ramanjaneya, Manjunath, Alex C. Conner, Jing Chen, et al. "Orexin-stimulated MAP kinase cascades are activated through multiple G-protein signalling pathways in human H295R adrenocortical cells: diverse roles for orexins A and B." Journal of Endocrinology 202, no. 2 (2009): 249–61. http://dx.doi.org/10.1677/joe-08-0536.

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Orexins A and B (ORA and ORB) are neuropeptide hormones found throughout the central nervous system and periphery. They are required for a host of physiological processes including mitogen-activated protein kinase (MAPK) regulation, steroidogenesis, appetite control and energy regulation. While some signalling mechanisms have been proposed for individual recombinant orexin receptors in generic mammalian cell types, it is clear that the peripheral effects of orexin are spatially and temporally complex. This study dissects the different G-protein signalling and MAPK pathways activated in a pluri
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Wang, Ying, An-Qi Chen, Yan Xue, et al. "Orexins alleviate motor deficits via increasing firing activity of pallidal neurons in a mouse model of Parkinson’s disease." American Journal of Physiology-Cell Physiology 317, no. 4 (2019): C800—C812. http://dx.doi.org/10.1152/ajpcell.00125.2019.

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Orexin is a peptide neurotransmitter released in the globus pallidus. Morphological evidence reveals that both orexin 1 receptor (OX1R) and orexin 2 receptor (OX2R) exist in the globus pallidus. Here we showed that bilateral microinjection of both orexin-A and orexin-B into the globus pallidus alleviated motor deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonian mice. Further in vivo extracellular single-unit recording revealed that the basal spontaneous firing rate of the globus pallidus neurons in MPTP parkinsonian mice was slower than that of normal mice. App
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Grandjean, Celia Mueller, Manon Kiry, Catherine Vaillant, Oliver Nayler, and John Gatfield. "059 Daridorexant: A dual, equipotent, and insurmountable antagonist of both orexin-1 and orexin-2 receptors." Sleep 44, Supplement_2 (2021): A25. http://dx.doi.org/10.1093/sleep/zsab072.058.

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Abstract Introduction The orexin neuropeptide–receptor system is a central sleep and wake regulator in the brain. The two orexin receptor subtypes, OX1R and OX2R, are expressed either alone or together in all major wake-promoting brain areas. OX1R and OX2R activation by orexins causes elevation of intracellular calcium, which enhances synaptic transmission in secondary, monoaminergic wake- and arousal-promoting neurotransmitter circuits. Orexin receptor antagonists represent a novel and specific treatment of insomnia, which is different from classical therapy that more broadly inhibits brain a
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16

Cadeddu, Ron-Patrick, Akos G. Czibere, Sebastian Büst, et al. "Neuropeptides Orexin A and B Are Funktionally Aktive in CD34+ Hematopoietic Stem and Progenitor Cells." Blood 114, no. 22 (2009): 4593. http://dx.doi.org/10.1182/blood.v114.22.4593.4593.

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Abstract Abstract 4593 Orexin receptors are involved in the regulation of sleep-wake-rhythm, food intake and energy homeostasis and it was still recently believed that their expression is restricted to the nervous system. But, during the last years orexin receptors have been detected in an increasing number of peripheral tissues. We have earlier found orexin receptor 1 and 2 expression on human CD34+ hematopoietic stem and progenitor cells. Still, the sources of their physiological ligands, the peptides orexin A and B, seemed so far to be restricted to the central nerve system. Ca2+-dependent
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Campbell, Erin J., Mitchell KRI Hill, Xavier J. Maddern, Shubo Jin, Terence Y. Pang, and Andrew J. Lawrence. "Orexin-1 receptor signaling within the lateral hypothalamus, but not bed nucleus of the stria terminalis, mediates context-induced relapse to alcohol seeking." Journal of Psychopharmacology 34, no. 11 (2020): 1261–70. http://dx.doi.org/10.1177/0269881120959638.

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Background: The lateral hypothalamic orexin (hypocretin) system has a well-established role in the motivation for reward. This has particular relevance to substance use disorders since orexin-1 receptors play a critical role in alcohol-seeking behavior, acting at multiple nodes in relapse-associated networks. Aims: This study aimed to further our understanding of the role of orexin-1 receptor signaling within the lateral hypothalamus and bed nucleus of the stria terminalis, specifically in context-induced relapse to alcohol-seeking following punishment-imposed abstinence. Methods: We trained i
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18

Imperatore, Roberta, and Luigia Cristino. "Role of Orexin-B/Orexin 2 receptor in myocardial protection." Clinical Science 133, no. 7 (2019): 853–57. http://dx.doi.org/10.1042/cs20181036.

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Abstract Emerging evidence attributes to orexins/hypocretins (ORs) a protective function in the regulation of cardiovascular responses, heart rate, and hypertension. However, little is known about any direct effect of orexins in the heart function. This is of special relevance considering that cardiovascular diseases, including myocardial infarction and heart failure, are one of the major causes of mortality in the world. In the article published in Clinical Science (2018) (vol. 132, 2547–2564), Patel and colleagues investigated the role of orexins in myocardial protection. Intriguingly, they
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Takano, Saeko, Setsuko Kanai, Hiroko Hosoya, Minoru Ohta, Hiroshi Uematsu, and Kyoko Miyasaka. "Orexin-A does not stimulate food intake in old rats." American Journal of Physiology-Gastrointestinal and Liver Physiology 287, no. 6 (2004): G1182—G1187. http://dx.doi.org/10.1152/ajpgi.00218.2004.

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Aging is associated with a progressive decrease in appetite and food intake. Both A and B orexins, expressed in specific neurons of the lateral hypothalamic area, have been implicated in the regulation of sleep and feeding. In this study, the stimulatory effect of intracerebroventricular administration of the orexins on food intake was compared between young (4-mo-old) and old (25- to 27-mo-old) male Wistar rats. A stainless steel cannula was implanted stereotactically into the left lateral ventricle. After a 7-day recovery period, different doses (0–30 nmol) of orexins were injected into the
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Samson, Willis K., Sara L. Bagley, Alastair V. Ferguson, and Meghan M. White. "Hypocretin/orexin type 1 receptor in brain: role in cardiovascular control and the neuroendocrine response to immobilization stress." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 292, no. 1 (2007): R382—R387. http://dx.doi.org/10.1152/ajpregu.00496.2006.

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Hypocretin/orexin acts pharmacologically in the hypothalamus to stimulate stress hormone secretion at least in part by an action in the hypothalamic paraventricular nucleus, where the peptide's receptors have been localized. In addition, orexin acts in the brain to increase sympathetic tone and, therefore, mean arterial pressure and heart rate. We provide evidence for the role of endogenously produced hypocretin/orexin in the physiological response to immobilization stress and identify the receptor subtype responsible for this action of the peptide. Antagonism of the orexin type 1 receptor (OX
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Bengtsson, Magnus W., Kari Mäkelä, Markus Sjöblom, et al. "Food-induced expression of orexin receptors in rat duodenal mucosa regulates the bicarbonate secretory response to orexin-A." American Journal of Physiology-Gastrointestinal and Liver Physiology 293, no. 2 (2007): G501—G509. http://dx.doi.org/10.1152/ajpgi.00514.2006.

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Presence of appetite-regulating peptides orexin-A and orexin-B in mucosal endocrine cells suggests a role in physiological control of the intestine. Our aim was to characterize orexin-induced stimulation of duodenal bicarbonate secretion and modulation of secretory responses and mucosal orexin receptors by overnight food deprivation. Lewis × Dark Agouti rats were anesthetized and proximal duodenum cannulated in situ. Mucosal bicarbonate secretion (pH stat) and mean arterial blood pressure were continuously recorded. Orexin-A was administered intra-arterially close to the duodenum, intraluminal
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Hirata, Shinichi, Nanako Nakayama, Yoshiaki Soejima та ін. "ODP335 Mutual Effects of Orexin and BMPs on Gonadotropin Expression by Mouse Gonadotrope LβT2 Cells". Journal of the Endocrine Society 6, Supplement_1 (2022): A502. http://dx.doi.org/10.1210/jendso/bvac150.1044.

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Abstract Orexins are neuropeptides that express primarily in the hypothalamus and are produced in two isoforms, orexin A and orexin B. There are two kinds of G protein coupled receptors, orexin type 1 (OX1R) and type 2 (OX2R) receptors. Orexin has been reported to have key roles on sleep-wake regulation and feeding behavior in the central nervous system, whereas its receptors are also expressed in peripheral tissues including the endocrine organs, and orexin affects the regulation of the endocrine system. In our previous experiments, we have revealed the impact of orexins on anterior pituitary
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Hoang, Q. V., D. Bajic, M. Yanagisawa, S. Nakajima, and Y. Nakajima. "Effects of Orexin (Hypocretin) on GIRK Channels." Journal of Neurophysiology 90, no. 2 (2003): 693–702. http://dx.doi.org/10.1152/jn.00001.2003.

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Orexins (hypocretins) are recently discovered excitatory transmitters implicated in arousal and sleep. Yet, their ionic and signal transduction mechanisms have not been fully clarified. Here we show that orexins suppress G-protein–coupled inward rectifier (GIRK) channel activity, and this suppression is likely to lead to neuronal excitation. Cultured neurons from the locus coeruleus (LC) and the nucleus tuberomammillaris (TM) were used, as well as HEK293A cells transfected with GIRK1 and 2, either human orexin receptor type 1 (OX1R) or type 2 (OX2R), mu opioid receptor and GFP cDNAs. In GTPγS-
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Wu, Fengzhi, Yuehan Song, Feng Li, et al. "Wen-Dan Decoction Improves Negative Emotions in Sleep-Deprived Rats by Regulating Orexin-A and Leptin Expression." Evidence-Based Complementary and Alternative Medicine 2014 (2014): 1–10. http://dx.doi.org/10.1155/2014/872547.

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Wen-Dan Decoction (WDD), a formula of traditional Chinese medicine, has been clinically used for treating insomnia for approximately 800 years. However, the therapeutic mechanisms of WDD remain unclear. Orexin-A plays a key role in the sleep-wake cycle, while leptin function is opposite to orexin-A. Thus, orexin-A and leptin may be important factors in sleep disorders. In this study, 48 rats were divided into control, model, WDD-treated, and diazepam-treated groups. The model of insomnia was produced by sleep deprivation (SD) for 14 days. The expressions of orexin-A, leptin, and their receptor
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Antunes, Vagner R., G. Cristina Brailoiu, Ernest H. Kwok, Phouangmala Scruggs, and Nae J. Dun. "Orexins/hypocretins excite rat sympathetic preganglionic neurons in vivo and in vitro." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 281, no. 6 (2001): R1801—R1807. http://dx.doi.org/10.1152/ajpregu.2001.281.6.r1801.

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The two recently isolated hypothalamic peptides orexin A and orexin B, also known as hypocretin 1 and 2, are reported to be important signaling molecules in feeding and sleep/wakefulness. Orexin-containing neurons in the lateral hypothalamus project to numerous areas of the rat brain and spinal cord including the intermediolateral cell column (IML) of the thoracolumbar spinal cord. An in vivo and in vitro study was undertaken to evaluate the hypothesis that orexins, acting on sympathetic preganglionic neurons (SPNs) in the rat spinal cord, increase sympathetic outflow. First, orexin A (0.3, 1,
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Mazzocchi, G., L. K. Malendowicz, L. Gottardo, F. Aragona, and G. G. Nussdorfer. "Orexin A Stimulates Cortisol Secretion from Human Adrenocortical Cells through Activation of the Adenylate Cyclase-Dependent Signaling Cascade." Journal of Clinical Endocrinology & Metabolism 86, no. 2 (2001): 778–82. http://dx.doi.org/10.1210/jcem.86.2.7233.

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Orexins A and B are two hypothalamic peptides that increase food intake and body weight and probably play a role in the sleep regulation. They act through two subtypes of G protein-coupled receptors, called OX1-R and OX2-R. OX1-R selectively binds orexin-A, whereas OX2-R is nonselective for both orexins. Orexins did not affect the in vitro secretion of either catecholamine or aldosterone from human adrenals. Conversely, orexin A, but not orexin B, concentration dependently increased basal cortisol secretion from dispersed adrenocortical cells; the maximal effective concentration was 10−8 mol/L
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Hellmann, Jan, Matthäus Drabek, Jie Yin, et al. "Structure-based development of a subtype-selective orexin 1 receptor antagonist." Proceedings of the National Academy of Sciences 117, no. 30 (2020): 18059–67. http://dx.doi.org/10.1073/pnas.2002704117.

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Orexins are neuropeptides that activate the rhodopsin-like G protein-coupled receptors OX1R and OX2R. The orexin system plays an important role in the regulation of the sleep-wake cycle and the regulation of feeding and emotions. The nonselective orexin receptor antagonist suvorexant has been the first drug on the market targeting the orexin system and is prescribed for the treatment of insomnia. Subtype-selective OX1R antagonists are valuable tools to further investigate the functions and physiological role of the OX1R in vivo and promising lead compounds for the treatment of drug addiction,
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Fujisawa, Satoshi, Motoshi Komatsubara, Naoko Tsukamoto-Yamauchi, et al. "Orexin A Enhances Pro-Opiomelanocortin Transcription Regulated by BMP-4 in Mouse Corticotrope AtT20 Cells." International Journal of Molecular Sciences 22, no. 9 (2021): 4553. http://dx.doi.org/10.3390/ijms22094553.

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Orexin is expressed mainly in the hypothalamus and is known to activate the hypothalamic–pituitary–adrenal (HPA) axis that is involved in various stress responses and its resilience. However, the effects of orexin on the endocrine function of pituitary corticotrope cells remain unclear. In this study, we investigated the roles of orexin A in pro-opiomelanocortin (POMC) transcription using mouse corticotrope AtT20 cells, focusing on the bone morphogenetic protein (BMP) system expressed in the pituitary. Regarding the receptors for orexin, type 2 (OXR2) rather than type 1 (OX1R) receptor mRNA wa
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Wacker, Daniel, and Bryan L. Roth. "An alerting structure: human orexin receptor 1." Nature Structural & Molecular Biology 23, no. 4 (2016): 265–66. http://dx.doi.org/10.1038/nsmb.3198.

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Zhang, Yanan, D. Perrey, N. German, B. P. Gilmour, Jun-Xu Li, and B. F. Thomas. "Development of selective orexin-1 receptor antagonists." Drug and Alcohol Dependence 140 (July 2014): e249-e250. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.690.

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31

Marcos, Pilar, and Rafael Coveñas. "Involvement of the Orexinergic System in Feeding." Applied Sciences 12, no. 1 (2021): 86. http://dx.doi.org/10.3390/app12010086.

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To know the processes involved in feeding, the dysregulation of hypothalamic neuropeptides promoting anorexigenic/orexigenic mechanisms must be investigated. Many neuropeptides are involved in this behavior and in overweight/obesity. Current pharmacological strategies for the treatment of obesity are unfortunately not very effective and, hence, new therapeutic strategies must be investigated and developed. Due to the crucial role played by orexins in feeding behavior, the aim of this review is to update the involvement of the orexinergic system in this behavior. The studies performed in experi
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Russo, F., G. Petrosino, and A. Vittoria. "Presence of orexin A and orexin 1 receptor in the buffalo prostate." Italian Journal of Animal Science 6, sup2 (2007): 794–95. http://dx.doi.org/10.4081/ijas.2007.s2.794.

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33

Aissaoui, Hamed, Ralf Koberstein, Cornelia Zumbrunn, et al. "N-Glycine-sulfonamides as potent dual orexin 1/orexin 2 receptor antagonists." Bioorganic & Medicinal Chemistry Letters 18, no. 21 (2008): 5729–33. http://dx.doi.org/10.1016/j.bmcl.2008.09.079.

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Samson, Willis K., and Meghan M. Taylor. "Hypocretin/orexin suppresses corticotroph responsiveness in vitro." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 281, no. 4 (2001): R1140—R1145. http://dx.doi.org/10.1152/ajpregu.2001.281.4.r1140.

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The hypocretin/orexins (Hcrts/ORXs) are peptides produced in neurons in the lateral hypothalamic area that project to neuroendocrine centers in the hypothalamus. Hcrt/ORX receptors are present in the hypothalamus and anterior pituitary gland. We examined the possibility that the Hcrts/ORXs, which we have demonstrated previously to act in the brain to stimulate sympathetic function, could alter stress hormone secretion by a direct pituitary action. In vitro studies revealed a dose-related inhibitory effect of the Hcrts/ORXs on corticotropin-releasing hormone-stimulated ACTH secretion that appea
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35

Kon, Kanta, Hiroshi Tsuneki, Hisakatsu Ito, et al. "Chronotherapeutic effect of orexin antagonists on glucose metabolism in diabetic mice." Journal of Endocrinology 243, no. 1 (2019): 59–72. http://dx.doi.org/10.1530/joe-18-0708.

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Disrupted sleep is associated with increased risk of type 2 diabetes. Central actions of orexin, mediated by orexin-1 and orexin-2 receptors, play a crucial role in the maintenance of wakefulness; accordingly, excessive activation of the orexin system causes insomnia. Resting-phase administration of dual orexin receptor antagonist (DORA) has been shown to improve sleep abnormalities and glucose intolerance in type 2 diabetic db/db mice, although the mechanism remains unknown. In the present study, to investigate the presence of functional link between sleep and glucose metabolism, the influenc
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36

Dugovic, Christine, Jonathan E. Shelton, Leah E. Aluisio, et al. "Blockade of Orexin-1 Receptors Attenuates Orexin-2 Receptor Antagonism-Induced Sleep Promotion in the Rat." Journal of Pharmacology and Experimental Therapeutics 330, no. 1 (2009): 142–51. http://dx.doi.org/10.1124/jpet.109.152009.

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37

Hilairet, Sandrine, Monsif Bouaboula, Dominique Carrière, Gérard Le Fur, and Pierre Casellas. "Hypersensitization of the Orexin 1 Receptor by the CB1 Receptor." Journal of Biological Chemistry 278, no. 26 (2003): 23731–37. http://dx.doi.org/10.1074/jbc.m212369200.

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38

Soejima, Yoshiaki, Nahoko Iwata, Nanako Nakayama, et al. "Mutual Effects of Orexin and Bone Morphogenetic Proteins on Gonadotropin Expression by Mouse Gonadotrope Cells." International Journal of Molecular Sciences 23, no. 17 (2022): 9782. http://dx.doi.org/10.3390/ijms23179782.

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Orexin plays a key role in the regulation of sleep and wakefulness and in feeding behavior in the central nervous system, but its receptors are expressed in various peripheral tissues including endocrine tissues. In the present study, we elucidated the effects of orexin on pituitary gonadotropin regulation by focusing on the functional involvement of bone morphogenetic proteins (BMPs) and clock genes using mouse gonadotrope LβT2 cells that express orexin type 1 (OX1R) and type 2 (OX2R) receptors. Treatments with orexin A enhanced LHβ and FSHβ mRNA expression in a dose-dependent manner in the a
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Dong, Hai-long, Satoru Fukuda, Eri Murata, Zhenghua Zhu, and Takashi Higuchi. "Orexins Increase Cortical Acetylcholine Release and Electroencephalographic Activation through Orexin-1 Receptor in the Rat Basal Forebrain during Isoflurane Anesthesia." Anesthesiology 104, no. 5 (2006): 1023–32. http://dx.doi.org/10.1097/00000542-200605000-00019.

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Background Cholinergic arousal system plays an important role in the maintenance of consciousness. The authors investigated whether the intrabasalis injection of orexin-A or orexin-B and the electrically stimulated pedunculopontine tegmentum nuclei (PPTg: the origin of cholinergic ascending pathways) may alter acetylcholine efflux and electroencephalographic activity in the somatosensory cortex in relation to the orexinergic system in isoflurane-anesthetized rats. Methods Either orexin-A (10, 30, or 100 pmol) or orexin-B (10, 30, or 100 pmol) (n = 6 each) was injected into the basal forebrain
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Krowicki, Zbigniew K., Melissa A. Burmeister, Hans-Rudolf Berthoud, Roisin T. Scullion, Kristine Fuchs, and Pamela J. Hornby. "Orexins in rat dorsal motor nucleus of the vagus potently stimulate gastric motor function." American Journal of Physiology-Gastrointestinal and Liver Physiology 283, no. 2 (2002): G465—G472. http://dx.doi.org/10.1152/ajpgi.00264.2001.

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Orexins regulate food intake, arousal, and the sleep-wake cycle. They are synthesized by neurons in the lateral hypothalamus and project to autonomic areas in the hindbrain. Orexin A applied to the dorsal surface of the medulla stimulates gastric acid secretion via a vagally mediated pathway. We tested the hypothesis that orexins in the dorsal motor nucleus (DMN) of the vagus regulate gastric motor function. Multibarelled micropipette assemblies were used to administer vehicle, l-glutamate, orexins A (1 and 10 pmol) and B (10 pmol), and a dye marker into this site in anesthetized rats. When th
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41

Cook, Chris, Nicolas Nunn, Amy A. Worth, et al. "The hypothalamic RFamide, QRFP, increases feeding and locomotor activity: The role of Gpr103 and orexin receptors." PLOS ONE 17, no. 10 (2022): e0275604. http://dx.doi.org/10.1371/journal.pone.0275604.

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Here we show that central administration of pyroglutamylated arginine-phenylamine-amide peptide (QRFP/26RFa) increases both food intake and locomotor activity, without any significant effect on energy expenditure, thermogenesis or reward. Germline knock out of either of the mouse QRFP receptor orthologs, Gpr103a and Gpr103b, did not produce a metabolic phenotype. However, both receptors are required for the effect of centrally administered QRFP to increase feeding and locomotor activity. As central injection of QRFP activated orexin/hypocretin neurons in the lateral hypothalamus, we compared t
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Chen, Yi-Hung, Hsin-Jung Lee, Ming Tatt Lee, et al. "Median nerve stimulation induces analgesia via orexin-initiated endocannabinoid disinhibition in the periaqueductal gray." Proceedings of the National Academy of Sciences 115, no. 45 (2018): E10720—E10729. http://dx.doi.org/10.1073/pnas.1807991115.

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Adequate pain management remains an unmet medical need. We previously revealed an opioid-independent analgesic mechanism mediated by orexin 1 receptor (OX1R)-initiated 2-arachidonoylglycerol (2-AG) signaling in the ventrolateral periaqueductal gray (vlPAG). Here, we found that low-frequency median nerve stimulation (MNS) through acupuncture needles at the PC6 (Neiguan) acupoint (MNS-PC6) induced an antinociceptive effect that engaged this mechanism. In mice, MNS-PC6 reduced acute thermal nociceptive responses and neuropathy-induced mechanical allodynia, increased the number of c-Fos–immunoreac
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Willie, Jon T., Richard M. Chemelli, Christopher M. Sinton, et al. "Distinct Narcolepsy Syndromes in Orexin Receptor-2 and Orexin Null Mice." Neuron 38, no. 5 (2003): 715–30. http://dx.doi.org/10.1016/s0896-6273(03)00330-1.

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44

Bengtsson, Magnus W., Kari Mäkelä, Karl-Heinz Herzig, and Gunnar Flemström. "Short food deprivation inhibits orexin receptor 1 expression and orexin-A induced intracellular calcium signaling in acutely isolated duodenal enterocytes." American Journal of Physiology-Gastrointestinal and Liver Physiology 296, no. 3 (2009): G651—G658. http://dx.doi.org/10.1152/ajpgi.90387.2008.

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Close intra-arterial infusion of the appetite regulating peptide orexin-A stimulates bicarbonate secretion from the duodenal mucosa. The aim of the present study was to elucidate the ability of orexin-A to induce intracellular calcium signaling in acutely isolated duodenal enterocytes. Freshly isolated clusters of enterocytes, obtained from rat duodenal mucosa or human duodenal biopsies, were loaded with fura 2-AM and mounted in a perfusion chamber. Cryptlike enterocytes were selected (caged), and changes in intracellular calcium concentration ([Ca2+]i) were evaluated by fluorescence imaging.
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Kambe, D., H. Hikichi, Y. Tokumaru, M. Ohmichi, Y. Konno, and N. Hino. "0004 TS-142: A Novel and Potent Dual Orexin Receptor Antagonist with Sleep-Promoting Effects in Rats." Sleep 43, Supplement_1 (2020): A2. http://dx.doi.org/10.1093/sleep/zsaa056.003.

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Abstract Introduction The orexin system plays a pivotal role in regulating sleep and wakefulness, thus, orexin receptors (OX1 and OX2 receptors) have gained much attention as promising therapeutic targets for the treatment of insomnia. We synthesized a novel and potent dual orexin receptor antagonist (DORA), ORN0829 (investigation code name as TS-142), which was designed to have short-acting effects. Here we report pharmacological and pharmacokinetic profiles of ORN0829 in rats. Methods The antagonistic activities of ORN0829 were assessed using calcium mobilization assays. Ala-orexin A-induced
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Perrey, David A., and Yanan Zhang. "Therapeutics development for addiction: Orexin-1 receptor antagonists." Brain Research 1731 (March 2020): 145922. http://dx.doi.org/10.1016/j.brainres.2018.08.025.

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47

Sellayah, Dyan, and Devanjan Sikder. "Orexin receptor-1 mediates brown fat developmental differentiation." Adipocyte 1, no. 1 (2012): 58–63. http://dx.doi.org/10.4161/adip.18965.

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48

Stump, Craig A., Andrew J. Cooke, Joseph Bruno, et al. "Discovery of highly potent and selective orexin 1 receptor antagonists (1-SORAs) suitable for in vivo interrogation of orexin 1 receptor pharmacology." Bioorganic & Medicinal Chemistry Letters 26, no. 23 (2016): 5809–14. http://dx.doi.org/10.1016/j.bmcl.2016.10.019.

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49

Smith, Rachel J., Ronald E. See, and Gary Aston-Jones. "Orexin/hypocretin signaling at the orexin 1 receptor regulates cue-elicited cocaine-seeking." European Journal of Neuroscience 30, no. 3 (2009): 493–503. http://dx.doi.org/10.1111/j.1460-9568.2009.06844.x.

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50

Darker, John G., Roderick A. Porter, Drake S. Eggleston, et al. "Structure–activity analysis of truncated orexin-A analogues at the orexin-1 receptor." Bioorganic & Medicinal Chemistry Letters 11, no. 5 (2001): 737–40. http://dx.doi.org/10.1016/s0960-894x(01)00043-9.

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