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cGMP Pathway (cgmp + pathway)
Selected AbstractsExogenous nitric oxide causes potentiation of hippocampal synaptic transmission during low-frequency stimulation via the endogenous nitric oxide,cGMP pathwayEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2001Christelle L. M. Bon Abstract Nitric oxide (NO) is a putative participant in synaptic plasticity and demonstrations that exogenous NO can elicit the same plastic changes have been taken to support such a role. The experiments, carried out on the CA1 region of rat hippocampal slices, were aimed at testing this interpretation. A major component of tetanus-induced long-term potentiation (LTP) was lost in response to l -nitroarginine, which inhibits NO synthase, and 1H -[1,2,4]oxadiazolo[4,3- a]quinoxalin-1-one (ODQ), which inhibits NO-sensitive soluble guanylyl cyclase (sGC). At 0.2 Hz afferent fibre stimulation, exogenous NO produced, concentration-dependently, a synaptic depression that reverted on washout to a persistent potentiation that occluded tetanus-induced LTP. The NO concentrations necessary (estimated in the 100-nm range), however, were mostly supramaximal for stimulating hippocampal slice sGC activity. Nevertheless the potentiation, but not the preceding depression, was blocked by ODQ. l -nitroarginine and an NMDA antagonist were similarly effective, indicating mediation by the endogenous NMDA receptor,NO synthase,sGC pathway. At a concentration normally too low to affect synaptic transmission but sufficient to stimulate sGC (estimated to be 50 nm), exogenous NO reversed the effect of l -nitroarginine and caused a potentiation which was blocked by ODQ. At a concentration inducing the depression/potentiation sequence, NO partially inhibited hippocampal slice oxygen consumption. It is concluded that, at physiological levels, exogenous NO can directly elicit a potentiation of synaptic transmission through sGC, provided that the synapses are suitably primed. At higher concentrations, NO inhibits mitochondrial respiration, which can result in an enduring synaptic potentiation due to secondary activation of the endogenous NO,cGMP pathway. [source] Differential regulation of the nitric oxide,cGMP pathway exacerbates postischaemic heart injury in stroke-prone hypertensive ratsEXPERIMENTAL PHYSIOLOGY, Issue 1 2007Tetsuji Itoh Using a working perfused heart model, we investigated the hypothesis that alterations in the NO,cGMP pathway may exacerbate postischaemic mechanical dysfunction in the hypertrophied heart. Ischaemia for 25 min followed by reperfusion for 30 min produced marked cardiac mechanical dysfunction in both stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar Kyoto rats (WKY). Exogenous treatment with S -nitroso- N -acetyl- dl -penicillamine (SNAP), a NO donor, had beneficial effects on the cardiac dysfunction induced by ischaemia,reperfusion (I/R) in the WKY heart, but the cardioprotective effect of SNAP was eliminated by guanylyl cyclase inhibitor. Cardiac cGMP levels were increased by SNAP or ischaemia in WKY. In contrast, in SHRSP hearts, SNAP could not alleviate the cardiac dysfunction caused by I/R. Pre-ischaemia, the cardiac cGMP level was significantly higher in SHRSP than in WKY; however, no significant difference was found after SNAP and ischaemia. The myocardial Ca2+ -dependent NO synthase (NOS) activity increased at the end of ischaemia in WKY. Conversely, the Ca2+ -independent NOS activity and protein levels were upregulated by I/R in the SHRSP myocardium. In the SHRSP hearts, non-selective NOS and selective Ca2+ -independent NOS inhibitors or antioxidant treatment alleviated cardiac dysfunction caused by I/R. Moreover, mRNA expression and Western blotting analysis of cGMP-dependent protein kinase type I showed more deterioration of SHRSP hearts compared with WKY. These results suggest that: (1) the NO-dependent cardioprotective effect is depressed; and (2) overproduction of NO derived from Ca2+ -independent NOS contributes to postischaemic heart injury in the hypertrophied heart of hypertensive status. [source] Endothelin A receptors mediate relaxation of guinea pig internal anal sphincter through cGMP pathwayNEUROGASTROENTEROLOGY & MOTILITY, Issue 9 2010S.-c. Huang Abstract Background, Endothelin (ET) modulates motility of the internal anal sphincter through unclear receptor subtypes. Methods, We measured relaxation of guinea pig internal anal sphincter strips caused by ET-related peptides and binding of 125I-ET-1 to cell membranes prepared from the internal anal sphincter muscle. Visualization of 125I-ET-1 binding sites in tissue was performed by autoradiography. Key Results , In the guinea pig internal anal sphincter, ET-1 caused a marked relaxation insensitive to tetrodotoxin, atropine, or ,-conotoxin GVIA. ET-2 was as potent as ET-1. ET-3 caused a mild relaxation. The relative potencies for ETs to cause relaxation were ET-1 = ET-2 > ET-3. The ET-1-induced relaxation was inhibited by BQ-123, an ETA antagonist, but not by BQ-788, an ETB antagonist. These indicate that ETA receptors mediate the relaxation. The relaxant response of ET-1 was attenuated by LY 83583, KT 5823, Rp-8CPT-cGMPS, tetraethyl ammonium, 4-aminopyridine and N(omega)-nitro-l-arginine, but not significantly affected by NG -nitro-l-arginine methyl ester, NG -methyl-l-arginine, charybdotoxin, apamin, KT 5720, and Rp-cAMPS. These suggest the involvement of cyclic guanosine 3,,5,-cyclic monophosphate (cGMP), and potassium channels. Autoradiography localized 125I-ET-1 binding to the internal anal sphincter. Binding of 125I-ET-1 to the cell membranes prepared from the internal anal sphincter revealed the presence of two subtypes of ET receptors, ETA and ETB receptors. Conclusions & Inferences, Taken together, these results demonstrate that ETA receptors mediate relaxation of guinea pig internal anal sphincter through the cGMP pathway. [source] Nitric oxide mediates the inhibitory effect of ethanol on the motility of isolated longitudinal muscle of proximal colon in ratsNEUROGASTROENTEROLOGY & MOTILITY, Issue 6 2007S. L. Wang Abstract, The aim of the present study was to investigate the effect of ethanol on colon motility in rats and to test the possibility that nitric oxide (NO) mediates this effect. Proximal colon longitudinal muscle strips (LM) (8 × 3 mm) cut parallel to the longitudinal muscle fibres of the colon were isolated and mounted in an organ bath. Ethanol (0.57, 0.87 and 1.30 mmol L,1) dose-dependently inhibited the motility of LM. Longitudinal muscle strips from female rats were more sensitive to the inhibitory effect of ethanol than that from male rats. L-NAME (N -nitro- l -arginine methyl ester) (100 ,mol L,1), AG (aminoguanidine) (10 ,mol L,1), ODQ (1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one) (10 ,mol L,1) and PTIO (2-Phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide) (200 ,mol L,1) partly blocked the inhibitory effect of ethanol on LM. Pretreatment with L-NAME, AG, ODQ and PTIO abolished the sex difference of the inhibitory effect of ethanol on LM. Tetrodotoxin (TTX) (10 ,mol L,1) partly blocked the inhibitory effect but did not influence the sex difference. The relaxation of LM induced by SNP (sodium nitroprusside) (0.1,10 ,mol L,1) in female rats was greater than that in male rats. In conclusion, ethanol inhibited the colon motility in vitro. This inhibitory effect on LM was mediated by NO through the iNOS , NO , cGMP pathway. [source] Microinjection of glutamate into dorsal motor nucleus of the vagus excites gallbladder motility through NMDA receptor , nitric oxide , cGMP pathwayNEUROGASTROENTEROLOGY & MOTILITY, Issue 3 2004C. Y. Liu Abstract, We have reported that both glutamate and nitric oxide (NO) participated in the regulation of gallbladder motility in dorsal motor nucleus of the vagus (DMV). The aim of this study is to investigate the type of receptor in DMV that mediates the excitatory effect of glutamate on gallbladder motility and the correlation between the glutamate and NO. A frog bladder connected with a force transducer was inserted into the gallbladder to record the change of gallbladder pressure. Glutamate (65 mmol L,1, 100 nL) microinjected into DMV significantly increased the strength of gallbladder phasic contraction. This effect was abolished by ketamine (180 mmol L,1, 100 nL), the specific N -methyl- d -aspartic acid (NMDA) receptor antagonist, but was not influenced by 6-cyaon-7-nitroquinoxaline-2,3-(1H,4H)-dione (CNQX) (180 mmol L,1, 100 nL), the non-NMDA ionotropic receptor antagonist. NG -nitro- l -arginine-emthyl (l -NAME) (1 mol L,1, 100 nL), the nitric oxide synthase (NOS) inhibitor, reversed the excitatory effect of glutamate on gallbladder motility. Microinjection of sodium nitroprusside (SNP), the NO donor, into DMV enhanced the gallbladder motility, and this effect was not modulated by ketamine. Microinjection of NMDA (5 mmol L,1, 100 nL) increased the strength of gallbladder phasic contraction, and this effect was attenuated by methylene blue (100 mmol L,1, 100 nL), the soluble guanylate cyclase inhibitor. These results suggest that glutamate regulate the gallbladder motility through the NMDA receptor , NO , cGMP pathway in DMV. [source] DOES NITRIC OXIDE MODULATE TRANSMITTER RELEASE AT THE MAMMALIAN NEUROMUSCULAR JUNCTION?CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 4 2007Travis J Nickels SUMMARY 1Application of the nitric oxide (NO) donor, sodium nitrite and the NO synthase substrate l -arginine had no effect on nerve-evoked transmitter release in the rat isolated phrenic nerve/hemidiaphragm preparation; however, when adenosine A1 receptors were blocked with the adenosine A1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) prior to application of sodium nitrate or l -arginine, a significant increase in transmitter release was observed. In addition, the NO donor s -nitroso- N -acetylpenicillamine (SNAP) significantly increased transmitter release in the presence of DPCPX. In the present study, we have made the assumption that these NO donors elevate the level of NO in the tissue. Future studies should test other NO-donating compounds and also monitor the NO concentrations in the tissue to ensure that these effects are, in fact, NO induced. 2Elevation of cGMP in this preparation with the guanylyl cyclase activator 3-(5,-hydroxymethyl-2,-furyl)-1-benzyl indazole (YC-1) significantly enhanced transmitter release. In the presence of DPCPX and the selective guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), which blocks the production of cGMP, the excitatory effects of sodium nitrite and l -arginine were abolished. 3These results suggest that NO serves to enhance transmitter release at the rat neuromuscular junction (NMJ) via a cGMP pathway and this facilitation of transmitter release can be blocked with adenosine. Previously, we demonstrated that adenosine inhibits N-type calcium channels. Because NO only affects transmitter release when adenosine A1 receptors are blocked, we suggest that NO enhances transmitter release by enhancing calcium influx via N-type calcium channels. Further studies are needed to confirm that NO alters transmitter release via cGMP and that this action involves the N-type calcium channel. 4The results of the present study are consistent with a model of NO neuromodulation that has been proposed for the mammalian vagal,atrial junction. This model suggests that NO acts on NO-sensitive guanylyl cyclase to increase the intracellular levels of cGMP. In turn, cGMP inhibits phosphodiesterase-3, increasing levels of cAMP, which then acts on the N-type calcium channels to enhance calcium influx, leading to an increase in transmitter release. Our only modification to this model for the NMJ is that adenosine serves to block the modulation of transmitter release by NO. [source] | |||||||||||||