Academic literature on the topic 'NO-cGMP pathway'
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Journal articles on the topic "NO-cGMP pathway"
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Denninger, John W., and Michael A. Marletta. "Guanylate cyclase and the ⋅NO/cGMP signaling pathway." Biochimica et Biophysica Acta (BBA) - Bioenergetics 1411, no. 2-3 (May 1999): 334–50. http://dx.doi.org/10.1016/s0005-2728(99)00024-9.
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YU, DOU, and WILLIAM D. ELDRED. "Gycine and GABA interact to regulate the nitric oxide/cGMP signaling pathway in the turtle retina." Visual Neuroscience 22, no. 6 (November 2005): 825–38. http://dx.doi.org/10.1017/s0952523805226123.
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Nitric oxide (NO) is a free radical that is important in retinal signal transduction and cyclic guanosine monophosphate (cGMP) is a critical downstream messenger of NO. The NO/cGMP signaling pathway has been shown to modulate neurotransmitter release and gap junction coupling in horizontal cells and amacrine cells, and increase the gain of the light response in photoreceptors. However, many of the mechanisms controlling the production of NO and cGMP remain unclear. Previous studies have shown activation of NO/cGMP production in response to stimulation with N-methyl-d-aspartate (NMDA) or nicotine, and the differential modulation of cGMP production by GABAA and GABAC receptors (GABAARs and GABACRs). This study used cGMP immunocytochemistry and NO imaging to investigate how the inhibitory GABAergic and glycinergic systems modulate the production of NO and cGMP. Our data show that blocking glycine receptors (GLYR) with strychnine (STRY) produced moderate increases in cGMP-like immunoreactivity (cGMP-LI) in select types of amacrine and bipolar cells, and strong increases in NO-induced fluorescence (NO-IF). TPMPA, a selective GABACR antagonist, greatly reduced the increases in cGMP-LI stimulated by STRY, but did not influence the increase in NO-IF stimulated by STRY. Bicuculline (BIC), a GABAAR antagonist, however, enhanced the increases in both the cGMP-LI and NO-IF stimulated by STRY. CNQX, a selective antagonist for α-Amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid hydrobromide/kainic acid (AMPA/KA) receptors, eliminated both the increases in cGMP-LI and NO-IF stimulated by STRY, while MK801, a selective antagonist for NMDA receptors, slightly increased the cGMP-LI and slightly decreased the NO-IF stimulated by STRY. Finally, double labeling of NO-stimulated cGMP and either GLY or GABA indicated that cGMP predominantly colocalized with GLY. Taken together, these findings support the hypothesis that GLY and GABA interact in the regulation of the NO/cGMP signaling pathway, where GLY primarily inhibits NO production and GABA has a greater effect on cGMP production. Such interacting inhibitory pathways could shape the course of signal transduction of the NO/cGMP pathway under different physiological situations.
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Frank, Deborah U., Damian J. Horstman, Geoffrey N. Morris, Roger A. Johns, and George F. Rich. "Regulation of the endogenous NO pathway by prolonged inhaled NO in rats." Journal of Applied Physiology 85, no. 3 (September 1, 1998): 1070–78. http://dx.doi.org/10.1152/jappl.1998.85.3.1070.
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Nitric oxide (NO) modulates the endogenous NO-cGMP pathway. We determined whether prolonged inhaled NO downregulates the NO-cGMP pathway, which may explain clinically observed rebound pulmonary hypertension. Rats were placed in a normoxic (N; 21% O2) or hypoxic (H; 10% O2) environment with and without inhaled NO (20 parts/million) for 1 or 3 wk. Subsequently, nitric oxide synthase (NOS) and soluble guanylate cyclase (GC) activity and endothelial NOS (eNOS) protein levels were measured. Perfusate cGMP levels and endothelium-dependent and -independent vasodilation were determined in isolated lungs. eNOS protein levels and NOS activity were not altered by inhaled NO in N or H rats. GC activity was decreased by 60 ± 10 and 55 ± 11% in N and H rats, respectively, after 1 wk of inhaled NO but was not affected after 3 wk. Inhaled NO had no effect on perfusate cGMP in N lungs. Inhaled NO attenuated the increase in cGMP levels caused by 3 wk of H by 57 ± 11%, but there was no rebound in cGMP after 24 h of recovery. Endothelium-dependent vasodilation was not altered, and endothelium-independent vasodilation was not altered (N) or slightly increased (H, 10 ± 3%) by prolonged inhaled NO. In conclusion, inhaled NO did not alter the endogenous NO-cGMP pathway as determined by eNOS protein levels, NOS activity, or endothelium-dependent vasodilation under N and H conditions. GC activity was decreased after 1 wk; however, GC activity was not altered by 3 wk of inhaled NO and endothelium-independent vasodilation was not decreased.
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YU, DOU, and WILLIAM D. ELDRED. "GABAAand GABACreceptor antagonists increase retinal cyclic GMP levels through nitric oxide synthase." Visual Neuroscience 20, no. 6 (November 2003): 627–37. http://dx.doi.org/10.1017/s0952523803206052.
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The nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signal transduction pathway plays a role in every retinal cell type. Previous studies have shown that excitatory glutamatergic synaptic pathways can increase cGMP-like immunoreactivity (cGMP-LI) in retina through stimulation of NO production, but little is known about the role of synaptic inhibition in the modulation of cGMP-LI. Gamma-amino-n-butyric acid (GABA) plays critical roles in modulating excitatory synaptic pathways in the retina. Therefore, we used GABA receptor antagonists to explore the role of GABAergic inhibitory synaptic pathways on the modulation of the NO/cGMP signal-transduction system. Cyclic GMP immunocytochemistry was used to investigate the effects of the GABA receptor antagonists bicuculline, picrotoxin, and (1,2,5,6-tetrahyropyridin-4-yl) methylphosphinic acid (TPMPA) on levels of cGMP-LI. Cyclic GMP-LI was strongly increased in response to the GABAAreceptor antagonist bicuculline, while the GABACreceptor antagonist TPMPA had little effect on cGMP-LI. The GABAA/GABACreceptor antagonist, picrotoxin, caused a moderate increase in cGMP-LI, which was mimicked by the combination of bicuculline and TPMPA. The nitric oxide synthase inhibitor, S-methyl-L-thiocitrulline (SMTC), blocked the increased cGMP-LI in response to stimulation with either bicuculline or picrotoxin. Treatments with either of the glutamate receptor antagonists (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801) or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) partially blocked the increases in cGMP-LI seen in response to bicuculline, but a combination of MK-801 and CNQX completely eliminated these increases. These results suggest that inhibitory synaptic pathways involving both types of GABA receptors work through excitatory glutamatergic receptors to regulate the NO/cGMP signal-transduction pathway in retina.
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Pérez-Sala, Dolores, Eva Cernuda-Morollón, Manuela Díaz-Cazorla, Fernando Rodríguez-Pascual, and Santiago Lamas. "Posttranscriptional regulation of human iNOS by the NO/cGMP pathway." American Journal of Physiology-Renal Physiology 280, no. 3 (March 1, 2001): F466—F473. http://dx.doi.org/10.1152/ajprenal.2001.280.3.f466.
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Nitric oxide (NO) and cGMP may exert positive or negative effects on inducible NO synthase (iNOS) expression. We have explored the influence of the NO/cGMP pathway on iNOS levels in human mesangial cells. Inhibition of NOS activity during an 8-h stimulation with IL-1β plus tumor necrosis factor (TNF)-α reduced iNOS levels, while NO donors amplified iNOS induction threefold. However, time-course studies revealed a subsequent inhibitory effect of NO donors on iNOS protein and mRNA levels. This suggests that NO may contribute both to iNOS induction and downregulation. Soluble guanylyl cyclase (sGC) activation may be involved in these effects. Inhibition of sGC attenuated IL-1β/TNF-α-elicited iNOS induction and reduced NO-driven amplification. Interestingly, cGMP analogs also modulated iNOS protein and mRNA levels in a biphasic manner. Inhibition of transcription unveiled a negative posttranscriptional modulation of the iNOS transcript by NO and cGMP at late times of induction. Supplementation with 8-bromo-cGMP (8-BrcGMP) reduced iNOS mRNA stability by 50%. These observations evidence a complex feedback regulation of iNOS expression, in which posttranscriptional mechanisms may play an important role.
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Hamid, S. A., M. Totzeck, C. Drexhage, I. Thompson, R. C. Fowkes, T. Rassaf, and G. F. Baxter. "NO/cGMP pathway in adrenomedullin mediated cardioprotection in mouse." Journal of Molecular and Cellular Cardiology 42, no. 6 (June 2007): S195. http://dx.doi.org/10.1016/j.yjmcc.2007.03.592.
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Morris, R., E. Southam, S. R. Gittins, J. Vente, and J. Garthwaite. "The NO-cGMP Pathway in Neonatal Rat Dorsal Horn." European Journal of Neuroscience 6, no. 5 (May 1994): 876–79. http://dx.doi.org/10.1111/j.1460-9568.1994.tb00998.x.
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Stojanovic, Aleksandra, Jasna A. Marjanovic, Viktor Brokovych, Randal A. Skidgel, Nissim Hay, and Xiaoping Du. "AKT Mediates Platelet Activation by Stimulating Nitric Oxide Synthesis and cGMP Elevation." Blood 106, no. 11 (November 16, 2005): 1652. http://dx.doi.org/10.1182/blood.v106.11.1652.1652.
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Abstract Phosphoinositide 3-kinase (PI3-K) and Akt play important roles in platelet activation. However, the downstream mechanisms for their roles are unclear. We have recently shown that nitric oxide (NO) synthase 3 (NOS3) and cGMP-dependent protein kinase stimulate platelet secretion and aggregation. Here we show that PI3-K-mediated Akt activation plays a critical role in agonist-stimulated platelet NO synthesis and cGMP elevation. Agonist-induced elevation of NO and cGMP was inhibited by Akt inhibitors and reduced in Akt-1 knockout platelets. Akt-1 knockout or Akt inhibitor-treated platelets showed reduced platelet secretion and aggregation in response to low concentrations of agonists, which can be reversed by low concentrations of sodium nitroprusside (SNP) or cGMP analogs. Similarly, PI3-K inhibitors diminished elevation of cGMP and also inhibited platelet secretion and the second-wave platelet aggregation, which was also partially reversed by cGMP analogs and by SNP. These results indicate that the NO-cGMP pathway is an important downstream mechanism mediating PI3-K and Akt signals leading to platelet secretion and aggregation. Conversely, the PI3-K-Akt pathway is a major upstream mechanism responsible for activating the NO-cGMP pathway. Thus, this study delineates a novel platelet activation pathway involving sequential activation of PI3-K, Akt, NOS3, sGC, and cGMP-dependent protein kinase.
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Paolillo, Michael, Stefanie Peters, Andrea Schramm, Jens Schlossmann, and Robert Feil. "Real-Time Imaging Reveals Augmentation of Glutamate-Induced Ca2+ Transients by the NO-cGMP Pathway in Cerebellar Granule Neurons." International Journal of Molecular Sciences 19, no. 8 (July 26, 2018): 2185. http://dx.doi.org/10.3390/ijms19082185.
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Dysfunctions of NO-cGMP signaling have been implicated in various neurological disorders. We have studied the potential crosstalk of cGMP and Ca2+ signaling in cerebellar granule neurons (CGNs) by simultaneous real-time imaging of these second messengers in living cells. The NO donor DEA/NO evoked cGMP signals in the granule cell layer of acute cerebellar slices from transgenic mice expressing a cGMP sensor protein. cGMP and Ca2+ dynamics were visualized in individual CGNs in primary cultures prepared from 7-day-old cGMP sensor mice. DEA/NO increased the intracellular cGMP concentration and augmented glutamate-induced Ca2+ transients. These effects of DEA/NO were absent in CGNs isolated from knockout mice lacking NO-sensitive guanylyl cyclase. Furthermore, application of the cGMP analogues 8-Br-cGMP and 8-pCPT-cGMP, which activate cGMP effector proteins such as cyclic nucleotide-gated cation channels and cGMP-dependent protein kinases (cGKs), also potentiated glutamate-induced Ca2+ transients. Western blot analysis failed to detect cGK type I or II in our primary CGNs. The addition of phosphodiesterase (PDE) inhibitors during cGMP imaging showed that CGNs degrade cGMP mainly via Zaprinast-sensitive PDEs, most likely PDE5 and/or PDE10, but not via PDE1, 2, or 3. In sum, these data delineate a cGK-independent NO-cGMP signaling cascade that increases glutamate-induced Ca2+ signaling in CGNs. This cGMP–Ca2+ crosstalk likely affects neurotransmitter-stimulated functions of CGNs.
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Su, Jun, Shengjun Zhang, James Tse, Peter M. Scholz, and Harvey R. Weiss. "Alterations in nitric oxide-cGMP pathway in ventricular myocytes from obese leptin-deficient mice." American Journal of Physiology-Heart and Circulatory Physiology 285, no. 5 (November 2003): H2111—H2117. http://dx.doi.org/10.1152/ajpheart.00316.2003.
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Leptin is a regulator of body weight and affects nitric oxide (NO) production. This study was designed to determine whether the myocardial NO-cGMP signal transduction system was altered in leptin-deficient obese mice. Contractile function, guanylyl cyclase activity, and cGMP-dependent protein phosphorylation were assessed in ventricular myocytes isolated from genetically obese (B6.V-Lepob) and age-matched lean (C57BL/6J) mice. There were no differences in baseline contraction between the lean and obese groups. After stimulation with the NO donor S-nitroso- N-acetyl-penicillamine (SNAP, 10–6and 10–5M) or a membrane-permeable cGMP analog 8-bromo-cGMP (8-Br-cGMP, 10–6and 10–5M), cell contractility was depressed. However, 8-Br-cGMP had significantly greater effects in obese mice than in lean controls with percent shortening reduced by 47 vs. 39% and maximal rate of shortening decreased by 46 vs. 36%. The negative effects of SNAP were similar between the two groups. Soluble guanylyl cyclase activity was not attenuated. This suggests that the activity of the cGMP-independent NO pathway may be enhanced in obesity. The phosphorylated protein profile of cGMP-dependent protein kinase showed that four proteins were more intensively phosphorylated in obese mice, which suggests an explanation for the enhanced effect of cGMP. These results indicate that the NO-cGMP signaling pathway was significantly altered in ventricular myocytes from the leptin-deficient obese mouse model.
Dissertations / Theses on the topic "NO-cGMP pathway"
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Picot, Joanna. "The NO-cGMP signalling pathway in the CNS of the pond snail Lymnaea stagnalis." Thesis, University of Sussex, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.363375.
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Ogunshola, Omolara O. "Molecular studies of the NO-cGMP signalling pathway in the desert locust Schistocerca gregaria." Thesis, University of Sussex, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.363369.
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Retief, Renché. "The role of the NO-cGMP pathway as a putative target in antidepressant action / Renché Retief." Thesis, North-West University, 2004. http://hdl.handle.net/10394/731.
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Depressive disorders are among the most frequent psychiatric diseases in the Western world
with prevalence between 9% and 18%. Poor compliance and inappropriate antidepressant
discontinuation invokes long-term morbidity, and appear linked to hippocampal shrinkage.
Despite major advances in pharmacological treatment of the illness over the past 3040 years,
currently available agents have distinct shortfalls both in clinical efficacy and in maintenance of
response. This implies a greater long-term morbidity with significant impact on the patient, the
patient's family as well as economic implications to health care managers and providers. The
major reason for this state of affairs is our poor understanding of the neurobiology of depression
and hence, of antidepressant (AD) action. AD drugs are thus not addressing the crucial
neurobiological target underlying the illness, and new strategies and treatments are urgently
needed. In recent years, depression has been associated with disturbances in excitotoxic
glutamatergic activity, yet this has not been systematically evaluated.
While the role of neurotransmitters such as serotonin, noradrenaline and dopamine has been
extensively studied, new evidence suggests a role for the unique neurotransmitter nitric oxide
(NO). Nitric oxide (NO), is activated by glutamatergic systems in various limbic and other
regions of the brain, and has recently also been implicated in anxiety and affective disorders. Of
special interest is the putative role of NO in cellular memory, synaptic plasticity and cell survival,
all-important processes in the neuropathology and neurodevelopment of depression.
Recent clinical studies have provided evidence of the role of the NO-pathway in depression,
while preclinical studies have demonstrated the anxiolytic and antidepressant actions of nitric
oxide synthase (NOS)-inhibitors. Moreover, NO interacts with other classical transmitters that
have a regulatory role on mood, particularly the monoamines, as well as glutamate and gammaaminobutyric
acid (GABA).
In the current study the role of the NO-cGMP pathway in AD action was investigated, after
chronic imipramine (IMI) and after IMI withdrawal, using a learned helplessness paradigm.
Behavioural changes, hippocampal NOS activity and cGMP accumulation was determined
together with pharmacological manipulation of the NO-cGMP pathway.
Chronic IMI, 15 mg/kg/day intraperitoneal (ip) administration induced a pronounced reduction in
swim immobility time in the forced swim test (FST), with no effect on horizontal or vertical
locomotor activity. These behavioural changes were accompanied by a significant reduction in
NOS enzyme activity and cGMP accumulation. In order to confirm the involvement of the NO-cGMP
pathway in the AD action of IMI, chronic (3 weeks) IMI treatment was followed by an
acute withdrawal of 7 days. Acute withdrawal, after chronic IMI treatment, resulted in a
significant increase in swim immobility time and an increase in NOS enzyme activity and cGMP
levels. In fact, NOS activity was raised above that of control, not just higher than the effect of
chronic IMI.
In order to assess the possible role of the NMDA-NO-cGMP pathway in AD withdrawal, the
NMDA receptor antagonist, memantine, and the NOS/guanylyl cyclase (GC) inhibitor,
methylene blue (MB), were administered during the 7 day IMI withdrawal period.
Memantine (5 mg/kg/d ip), during the 7 day IMI withdrawal period, significantly reversed the
increase in immobility time evoked after IMI withdrawal. This was accompanied by a significant
reduction in NOS enzyme activity and a tendency to decrease cGMP levels. This data confirms
that the antidepressant action of IMI, as well as IMI withdrawal, is associated with actions on the
NMDA-GIu-NO-cGMP pathway. Particularly. IMI withdrawal evokes an increase in glutamate
activity that is responsible for NOS activation.
During the 7 day IMI withdrawal period, MB (15 mg/kg/d ip) also significantly reversed the
increased immobility time after IMI withdrawal and was accompanied by a tendency to decrease
NOS enzyme activity and cGMP levels in the rat hippocampus, however statistical significance
was not reached. Although not emphatic, this data implies a possible role of the NO-cGMP
pathway in AD action and AD withdrawal.
In order to determine whether the observed IMI withdrawal effects on the NO-cGMP pathway
may occur through an initial destabilisation in the serotonergic system, the 5-HT2a/2c receptor
antagonist, ritanserin (4 mg/kg/d ip), was administered during the IMI withdrawal period.
These studies revealed that antidepressant withdrawal evokes an increase in 5-HT2-mediated
activity, and that antidepressant-induced NOS activation after withdrawal has its origin in
serotonergic hyperactivity. Clearly, this is supportive of a distinct relationship between the NO
and serotonergic system in antidepressant response. On its own, ritanserin was found to
increase NOS and cGMP levels, yet during IMI withdrawal this response was lost, suggesting
that IMI withdrawal alters the response to a 5-HT2a/2c receptor antagonist, which may have major
clinical implications.
In conclusion, the AD action of IMI, as well as chronic IMI withdrawal, involves actions on the
NO-cGMP pathway. Withdrawal of ADS is associated with a loss of AD efficacy together with an
increase in release of NO and cGMP. The NMDA antagonist, memantine, and the NOS/GC
inhibitor, MB, reversed these responses therefore suggesting that the NMDA-GIu-NO-cGMP
pathway may be a new putative target in understanding the neurobiology of AD action. Finally,
NOS activation following withdrawal suggest that inappropriate withdrawal during the treatment
of depression may mediate neurodegenerative pathology observed in recurrent depression,
possibly by severely increased hippocampal NOS activity which is toxic to neurons.Thesis (M.Sc. (Pharmacology))--North-West University, Potchefstroom Campus, 2005.
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Slabbert, Francois Naudé. "The effect of acute and chronic sildenafil treatment with and without atropine co-administration on anxiety-like behaviour in rats / Francois Naudé Slabbert." Thesis, North-West University, 2010. http://hdl.handle.net/10394/8424.
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The neurobiology of anxiety-related disorders is associated with impaired neuroplasticity. The glutamate/NO/cGMP pathway has been proposed to play a key role in neuroplasticity and neurodevelopment. It was demonstrated in recent reports that chronic co-administration of the phosphodiesterase type 5 (PDE5) inhibitor sildenafil and the antimuscarinic agent atropine exerts antidepressive-like activity in rats, and that this effect is related to PDE5 inhibition, with consequent elevation of cGMP levels and enhanced protein kinase G stimulation.
The current study investigated possible anxiolytic effects of the chronic co-administration of sildenafil and atropine in stress-sensitive Flinders Sensitive Line (FSL) rats. FSL rats received vehicle control, fluoxetine (15 mg/kg), atropine (1 mg/kg), sildenafil (10 mg/kg) or sildenafil plus atropine via intraperitoneal administration, either acutely 30 minutes prior to testing (acutely) or daily for 14 days (chronically). FRL control rats received only vehicle. Thereafter anxiety-like behaviour was evaluated in the social interaction test (SIT - acute) and elevated plus maze (EPM - acute and chronic). The current study also compared to different ways to score the EPM, namely the percentage time spend in the open arms of the EPM and both the number of full and half body open arm entries, and also implemented defecation on the EPM as a measure of anxiety.
Vehicle-treated FSL rats exhibited more anxiety-like behaviour than FRL rats in both the SIT and EPM following acute treatment, and in the EPM following chronic treatment. Acute treatment with fluoxetine exerted anxiogenic activity in the SIT and EPM, but anxiolytic activity following chronic administration, as observed in the EPM. In acute treatments neither sildenafil nor sildenafil plus atropine yielded any significant effects on anxiety-like behaviour. However, following chronic treatment, sildenafil exerted anxiolytic activity in the EPM by increasing the time spend in the open arms (45.72% ± 9.94% vs. 20.80% ± 9.94%, P<0.001). Atropine exerted a small anxiolytic response (30.71% ± 8.40% vs. 20.80 ± 9.94%), whereas atropine co-administration was additive to sildenafil alone and yielded an enhanced anxiolytic effect in the elevated plus maze (59.56% ± 4.95% vs. 20.80% ± 9.94%, P<0.001), relative to vehicle control. The percentage time spend in the open arms was scored in the EPM, the results suggested that the chronic treatment with sildenafil plus atropine exert an anxiolytic-like effect in FSL rats and the number of fecal droppings did not increase which is also an indication of an anxiolytic-like effects of the treatment.
The current study demonstrated that the chronic treatment with sildenafil, alone or in combination with atropine, exhibit an anxiolytic-like action in stress-sensitive rats. In addition, the data support the clinical potential of using PDE5 inhibitors as antidepressant and anxiolytic strategy and warrant further investigation. Furthermore the study supports the previously proposed key role of the glutamate/NO/cGMP pathway in the neurobiology of anxiety-like disorders, and as an important target for drug development.Thesis (M.Sc. (Pharmacology))--North-West University, Potchefstroom Campus, 2011
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Bothma, Tanya. "Investigating the role of the NO-cGMP pathway in an animal model of posttraumatic stress disorder (PTSD) / Tanya Bothma." Thesis, North-West University, 2004. http://hdl.handle.net/10394/477.
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Posttraumatic stress disorder (PTSD) is a severe anxiety disorder characterised by
hypothalamic-pituitary-adrenal (HPA)-axis abnormalities, hyperarousal, anxiety,
flashbacks of trauma memories and avoidance. Increasing evidence is now
accumulating that the disorder is also associated with shrinkage of the hippocampus
and cognitive dysfunction that may have its origin in stress-induced excitotoxicity.
Animal studies have indeed highlighted a potential role of the excitotoxic glutamatenitric
oxide (NO) pathway in the stress response. Since PTSD appears to be an
illness that progresses and worsens over time after an initial severe traumatic event,
this study has used an animal model that emphasises repeated trauma to investigate
the effect of stress on hippocampal NO synthase (NOS) activity, the release of the
nitrogen oxide metabolites of NO (NOx), and also the evoked release of cGMP.
Furthermore, the modulation and dependency of these responses on glutamate, NO
and cGMP activity using drugs selective for these targets, will also be investigated.
Rats (n=10/group) were exposed to repeated stress together with saline or drug
administration immediately after the stress procedure and continuing for one week
post-stress. The animals were then sacrificed for assay of hippocampal NOS activity,
NO, and cGMP accumulation. Animals received either the glutamate-NMDA receptor
antagonist, memantine (MEM;5mg/kg ip/d), the neuronal NOS selective inhibitor, 7-
nitroindazole monosodium salt (7-NINA;20mg/kg ip/d), the cGMP-specific PDE
inhibitor, sildenafil (SIL;10mg/kg ip/d) or the NFkb antagonist, pyrollidine
dithiocarbamate (PDTC;70mg/kg ip/d). The latter inhibits the nuclear transcription
factor, NFkb, responsible for inducing the expression of iNOS, while it also appears
to mediate the glutamatergic actions on NOS expression,
Stress significantly increased hippocampal NOS activity, as well as significantly
increased hippocampal cGMP and NO, levels. These increases were blocked by pretreatment
with either PDTC or 7-NINA, while memantine was without effect. Sildenafil
significantly augmented stress induced NO, accumulation, as well as cGMP.
although the latter failed to reach significance. 7-NINA and memantine significantly
blocked the increase in cGMP evoked by time-dependent sensitisation (TDS)-stress,
with PDTC attenuating this response, but not significantly. Additionally, administration
of each drug separately for seven days without exposure to stress, did not evoke
significant changes in NOx levels, compared to the control group. However,
significant increases in cGMP levels, compared to the control group, were found with
all four drugs.
Repeated trauma therefore activates the NO-cGMP pathway, possibly involving
actions on both nNOS and iNOS. The NMDA receptor appears less involved after
chronic repeated stress, and may have limited therapeutic implications. Sub-cellular
NO-modulation, however, may represent an important therapeutic strategy in
preventing the effects of severe stress and in treating PTSD.Thesis (M.Sc. (Pharmacology))--North-West University, Potchefstroom Campus, 2005.
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Holmberg, Kristina. "Expression and regulation of neuronal messenger molecules : focus on the NO-cGMP pathway and galanin in autonomic and sensory neurons /." Stockholm, 2001. http://diss.kib.ki.se/2001/91-628-4909-3/.
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Medeiros, Mariana Siqueira de. "Efeitos do tratamento periodontal não-cirúrgico na via L-arginina-óxido nítrico e no estresse oxidativo em plaquetas." Universidade do Estado do Rio de Janeiro, 2011. http://www.bdtd.uerj.br/tde_busca/arquivo.php?codArquivo=3486.
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Universidade do Estado do Rio de JaneiroEstudos publicados nas duas últimas décadas sugerem um aumento do risco de doença cardiovascular (DCV) em pacientes com periodontite, mas os mecanismos fisiopatológicos dessa associação ainda não estão completamente esclarecidos. Uma vez que foi demonstrado aumento da ativação plaquetária e do estresse oxidativo na periodontite, o objetivo do presente estudo foi investigar a via L-arginina-óxido nítrico (NO)- guanosina monofosfato cíclica (GMPc) e parâmetros de estresse oxidativo em plaquetas de pacientes com periodontite, bem como avaliar o efeito do tratamento periodontal não-cirúrgico nessas variáveis. Um total de 10 pacientes sem periodontite (periodontalmente saudáveis ou com gengivite) e 10 pacientes com periodontite participaram do estudo. A avaliação clínica, laboratorial e experimental foi realizada no início do estudo e 90 dias após realização da terapia periodontal básica (grupo periodontite). A avaliação clínica periodontal incluiu registros de: profundidade de bolsa à sondagem (PBS), nível de inserção (NIC), percentual de placa e percentual de sangramento à sondagem. Os seguintes experimentos foram realizados: influxo de L-arginina; atividade e expressão das enzimas óxido nítrico sintase e da arginase; expressão das enzimas guanilato ciclase solúvel e fosfodiesterase 5; determinação dos níveis intraplaquetários de GMPc; agregação plaquetária; avaliação do estresse oxidativo (atividade oxidante total, atividade das enzimas antioxidantes catalase e da superóxido dismutase - SOD); medição dos níveis de proteína C reativa (CRP) e de fibrinogênio. Os resultados obtidos no início do estudo demonstraram ativação do influxo de L-arginina em plaquetas via sistema y+L nos pacientes com periodontite, bem como concentrações intraplaquetárias de GMPc diminuídas e aumento sistêmico da CRP. Após o tratamento periodontal, observou-se redução do percentual de sítios com PBS ≥ 6 mm, NIC 4-5 mm e NIC ≥ 6 mm, aumento nos níveis de GMPc, para níveis comparáveis aos dos pacientes sem periodontite, acompanhado por uma maior atividade das enzimas antioxidantes SOD e catalase. Os demais parâmetros avaliados não apresentaram alterações significativas tanto pré- quanto pós-tratamento. Esses resultados considerados em conjunto sugerem uma menor biodisponibilidade de NO em plaquetas na periodontite e que o tratamento periodontal não-cirúrgico foi capaz de reverter este quadro por um aumento das defesas antioxidantes. Portanto, alterações na via L-arginina-NO-GMPc e no estresse oxidativo podem levar à disfunção plaquetária, que poderia contribuir para um maior risco de DCV nos pacientes com periodontite.
Studies published over the last two decades have suggested an increase of cardiovascular disease (CVD) risk on periodontitis patients, but the physiopathological mechanisms involved in this association are not yet clear. Since it has been demonstrated an enhancement on both platelet activation and oxidative stress on periodontitis patients, the aim of this study was to investigate the L-arginine-nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) pathway on platelets from periodontitis patients, and the effect of non-surgical periodontal treatment in these variables. A total of 10 patients without periodontitis (periodontal healthy controls or gingivitis patients) and 10 periodontitis patients were included in this study. The clinical, laboratorial, and experimental evaluations were performed at the beginning of the study and 90 days after the basic periodontal therapy (periodontitis group). The clinical periodontal evaluation included the measurements of probing pocket depth (PPD), clinical attachment level (CAL), plaque percentage, and percentage of bleeding on probing. The following experiments were performed: L-arginine influx; nitric oxide synthase and arginase enzymes activity and expression; expression of guanylate cyclase and phosphodiesterase-5 enzymes; measurement of intraplatelet cGMP levels; platelet aggregation; oxidative stress evaluation (total oxidant activity and activity of both antioxidant enzymes catalase and superoxide dismutase SOD); measurement of C reactive protein (CRP) and fibrinogen. The initial results demonstrated an activation of L-arginine influx in platelets from periodontitis patients via y+L system, reduced intraplatelet cGMP levels and increased CRP. After periodontal treatment, it was observed reduction on percentage of sites with PPD ≥ 6 mm, CAL 4-5 mm and CAL ≥ 6 mm, enhancement on cGMP levels, to levels comparables to patients without periodontitis, accompanied by a higher activity of both antioxidant enzymes SOD and catalase. The other evaluated parameters did not showed significant alterations before and after periodontal treatment. The present results suggested a decreased NO biodisponibility in platelets from periodontitis patients and that the non-surgical periodontal treatment was effective to revert this condition, due to an enhancement on antioxidant defence. Therefore, alterations on L-arginine-NO-cGMP pathway and oxidative stress may lead to platelet dysfunction, which could contribute to a higher risk of CVD in periodontitis patients.
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Schaffner, Denise [Verfasser], and Irmgard [Akademischer Betreuer] Merfort. "Investigations of hepatic hemodynamics and alterations in the NO-cGMP pathway in an animal model of liver fibrosis / cirrhosis suggest PDE5 inhibitors as promising adjunct in portal hypertension therapy." Freiburg : Universität, 2018. http://d-nb.info/1189583216/34.
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Moughaizel, Michelle. "Metabolic and cardiovascular effects of nitric oxide-cyclic guanosine monophosphate (NO-cGMP) signaling pathway modulation : Study in the WHHL rabbit as an experimental model of high fructose high fat diet-induced metabolic syndrome." Thesis, Nantes, Ecole nationale vétérinaire, 2020. http://www.theses.fr/2020ONIR151F.
Full textAbstract:
Le syndrome métabolique (SMet) est caractérisé par la présence chez le même individu de plusieurs anomalies parmi les suivantes: une adiposité abdominale, une insulino-résistance (IR), une intolérance au glucose, une hypertension artérielle et une dyslipidémie. Des études ont révélé que la modulation de la voie de signalisation NO/GMPc dans le SMet peut exercer des effets métaboliques et cardiovasculaires protecteurs. Nous avons exploré, dans ce contexte, l'effet du mirabegron et du BAY 41-2272, deux molécules connues pour leur capacité à activer la voie NO-GMPc. Nous avons d'abord développé un modèle animal expérimental avec deux facteurs principaux du SMet, la dyslipidémie et l’IR. Nos résultats ont montré qu'après 12 semaines d'alimentation riche en fructose et en graisses (HFFD), le lapin Watanabe (WHHL), un modèle animal de dyslipidémie spontanée, présentait une intolérance au glucose, une IR (test HOMA-IR), une aggravation de la dyslipidémie et une diminution de la contractilité cardiaque (approche ex-vivo). Après 12 semaines de traitement, le mirabegron et le BAY 41-2272 ont prévenu le gain de poids et l’augmentation du taux de TG et ont amélioré la sensibilité à l'insuline, la fonction endothéliale des artères carotides et la fonction cardiaque (mirabegron). Ce travail a permis de mettre en place un modèle expérimental combinant la dyslipidémie et l’IR chez le lapin WHHL. De plus, les résultats ont montré que l'activation à long terme de la voie de signalisation NO-GMPc représente une approche pharmacologique prometteuse dans la gestion des complications métaboliques et cardiovasculaires associées au SMetMetabolic syndrome (MetS) is characterized by abdominal adiposity, insulin resistance (IR), glucose intolerance, arterial hypertension and dyslipidemia. Experimental studies have revealed that modulation of the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) signaling pathway in MetS can exert protective metabolic and cardiovascular effects. In this regard, we explored the effect of mirabegron and BAY 41-2272, two molecules known for their ability to activate the NO-cGMP pathway. We first developed an experimental animal model with two main components of the MetS, dyslipidemia and IR. Our results showed that after 12 weeks of high-fructose high-fat diet (HFFD) feeding, the Watanabe heritable hyperlipidemic (WHHL) rabbit, an animal model of spontaneous dyslipidemia, exhibited glucose intolerance, IR (HOMA-IR test), an aggravation in dyslipidemia and a decrease in cardiac contractility (ex-vivo approach). Twelve weeks of mirabegron and BAY 41-2272 treatment prevented weight gain and the increase in TG levels and improved insulin sensitivity, carotid endothelial function, and cardiac function (mirabegron). We were able to develop an experimental model combining dyslipidemia and IR in the WHHL rabbit. Furthermore, our results showed that long-term activation of the NO-cGMP signaling pathway represents a promising pharmacological approach in the management of the MetS and its metabolic and cardiovascular consequences
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Lukowski, Robert [Verfasser]. "Control of vasculo-proliferative processes by the NO-cGMP-cGKI pathway / Robert Lukowski." 2006. http://d-nb.info/98517773X/34.
Full textBook chapters on the topic "NO-cGMP pathway"
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Watanabe, Hiroshi, and Quang-Kim Tran. "Targeting the NO-sGC-cGMP Pathway in Pulmonary Arterial Hypertension." In Diagnosis and Treatment of Pulmonary Hypertension, 139–51. Singapore: Springer Singapore, 2017. http://dx.doi.org/10.1007/978-981-287-840-3_11.
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Brüne, B., S. Mohr, and U. K. Messmer. "Protein thiol modification and apoptotic cell death as cGMP-independent nitric oxide (NO) signaling pathways." In Reviews of Physiology, Biochemistry and Pharmacology, 1–30. Berlin, Heidelberg: Springer Berlin Heidelberg, 1995. http://dx.doi.org/10.1007/bfb0048263.
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Araújo, João Ronielly Campêlo, and Ana Cristina de Oliveira Monteiro-Moreira. "Depression and the NMDA receptor/NO/cGMP pathway." In The Neuroscience of Depression, 179–87. Elsevier, 2021. http://dx.doi.org/10.1016/b978-0-12-817935-2.00017-9.
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Fajmut, Aleš. "Molecular Mechanisms and Targets of Cyclic Guanosine Monophosphate (cGMP) in Vascular Smooth Muscles." In Muscle Cell and Tissue - Novel Molecular Targets and Current Advances [Working Title]. IntechOpen, 2021. http://dx.doi.org/10.5772/intechopen.97708.
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Molecular mechanisms and targets of cyclic guanosine monophosphate (cGMP) accounting for vascular smooth muscles (VSM) contractility are reviewed. Mathematical models of five published mechanisms are presented, and four novel mechanisms are proposed. cGMP, which is primarily produced by the nitric oxide (NO) dependent soluble guanylate cyclase (sGC), activates cGMP-dependent protein kinase (PKG). The NO/cGMP/PKG signaling pathway targets are the mechanisms that regulate cytosolic calcium ([Ca2+]i) signaling and those implicated in the Ca2+-desensitization of the contractile apparatus. In addition to previous mathematical models of cGMP-mediated molecular mechanisms targeting [Ca2+]i regulation, such as large-conductance Ca2+-activated K+ channels (BKCa), Ca2+-dependent Cl− channels (ClCa), Na+/Ca2+ exchanger (NCX), Na+/K+/Cl− cotransport (NKCC), and Na+/K+-ATPase (NKA), other four novel mechanisms are proposed here based on the existing but perhaps overlooked experimental results. These are the effects of cGMP on the sarco−/endo- plasmic reticulum Ca2+-ATPase (SERCA), the plasma membrane Ca2+-ATPase (PMCA), the inositol 1,4,5-trisphosphate (IP3) receptor channels type 1 (IP3R1), and on the myosin light chain phosphatase (MLCP), which is implicated in the Ca2+-desensitization. Different modeling approaches are presented and discussed, and novel model descriptions are proposed.
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Wu, Chieh-Hsi, Chun-Hsu Pan, and Ming-Jyh Sheu. "Therapeutic Applications and Mechanisms of YC-1: A Soluble Guanylate Cyclase Stimulator." In Vascular Biology - Selection of Mechanisms and Clinical Applications. IntechOpen, 2020. http://dx.doi.org/10.5772/intechopen.84572.
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Nitric oxide (NO) is an essential endogenous vasodilator to maintain vascular homeostasis, whose effects are mainly mediated by NO-dependent soluble guanylate cyclase (sGC) which catalyzes the synthesis of cyclic guanosine monophosphate (cGMP), a critical mediator of vascular relaxation. YC-1, a novel NO-independent sGC stimulator, was first introduced as an inhibitor of platelet aggregation and thrombosis. Accumulating studies revealed that YC-1 has multiple medication potentials to use for a broad spectrum of diseases ranging from cardiovascular diseases to cancers. In contrast to NO donors, YC-1 has a more favorable safety profile and low medication tolerance. In this chapter, we introduce canonical and pathological roles of NO, review activations, and regulatory mechanisms of YC-1 on NO-independent sGC/cGMP pathway and present the potential pharmacological applications and molecular mechanisms of YC-1.
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Fiorito, Jole, Shi-Xian Deng, Donald W. Landry, and Ottavio Arancio. "Targeting the NO/cGMP/CREB Phosphorylation Signaling Pathway in Alzheimer’s Disease." In Neurochemical Basis of Brain Function and Dysfunction. IntechOpen, 2019. http://dx.doi.org/10.5772/intechopen.81029.
Full textConference papers on the topic "NO-cGMP pathway"
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Caporarello, N., J. A. Meridew, A. Haresi, K. M. Choi, S. A. Austin, A. Aravamudhan, A. J. Haak, et al. "Vascular Dysfunction in Aged Mice Contributes to Persistent Lung Fibrosis Through the Impairment of the NO/sGC/cGMP Pathway." In American Thoracic Society 2020 International Conference, May 15-20, 2020 - Philadelphia, PA. American Thoracic Society, 2020. http://dx.doi.org/10.1164/ajrccm-conference.2020.201.1_meetingabstracts.a4387.
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Robinson, James, Chris Gartin, Joe H. Sisson, and Todd A. Wyatt. "Alcohol Decreases RhoA Activity Through A Nitric Oxide (NO)/Cyclic GMP(cGMP)/ Protein Kinase G (PKG) Dependent Pathway In The Airway Epithelium." In American Thoracic Society 2010 International Conference, May 14-19, 2010 • New Orleans. American Thoracic Society, 2010. http://dx.doi.org/10.1164/ajrccm-conference.2010.181.1_meetingabstracts.a6377.
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Grant, P. G., A. F. Mannarino, and R. W. Colman. "REGULATION OF CYCLIC NUCLEOTIDE PHOSPHODIESTERASE ACTIVITY IN PLATELETS BY PHOSPHORYLATION." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1642820.
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Cyclic nucleotide phosphodiesterases (PDE) provide the only known pathway for the hydrolysis of cyclic nucleotides in cells and thus have the potential for modulating the effects of cAMP and cGMP on cells. In platelets a rise in intracellular cAMP levels inhibits platelet aggregation and secretion. Since cAMP exerts many of its effects through a cAMP-dependent kinase we questioned whether phosphorylation of cAMP PDE might be a mode for regulation of PDE activity in platelets. When platelets were incubated for 10 min with forskolin (100 μM) the level of cAMP rose at least 10-fold.When the low Km cyclic nucleotide PDE was isolated from freeze-thaw lysates of forskolin treated platelets by chromatography on blue dextran-Sepharose, the specific activity of this enzyme was increased 3 to 13-fold over similarly processed control platelets. The specific activity of a second PDE, the cGMP-stimulated cAMP PDE, was increased 1.5 to 3-fold by forskolin treatment of platelets. Forskolin had no direct effect on either purified PDE. The stimulation of the low Km cAMP PDE activity by exposure of platelets to forskolin was blocked when the platelets were simultaneously treated with the protein kinase inhibitor H-8 (100 μM) which is most potent toward cAMP dependent protein kinase indicating that this kinase may be responsible for the stimulation. When platelets which had been prelabeled with 32P inorganic phosphate were treated with forskolin and the low Km cAMP PDE isolated by blue dextran-Sepharose chromatography, a protein migrating in SDS gels at Mr=110,000, the molecular weight of the low Km cAMP PDE, was labeled indicating that phosphorylation of the PDE occurred coincident with stimulation of activity. These results suggest that phosphorylation of the low Km cAMP PDE by protein kinase may be an important regulatory mechanism for cAMP PDE activity and cyclic nucleotide levels in platelets.