Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:4.6.1.2 (guanylate cyclase)
8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transmural electrical stimulation and nicotine produced a relaxation of dog cerebral artery strips denuded of endothelium, which was abolished by tetrodotoxin and hexamethonium, respectively, and also suppressed by treatment with NG-nitro-L-arginine (L-NA), a nitric oxide (NO) synthesis inhibitor. The inhibition was reversed by L-arginine but not by the D-enantiomer. L-NA also suppressed the endothelium-dependent relaxation by substance P but not the response to NO and nitroglycerin. Treatment with high concentrations of nitroglycerin or sodium nitroprusside markedly inhibited the relaxant response to nicotine, substance P and NO but not the response to papaverine. Slight, slowly developing relaxations caused by L-arginine in the endothelium-denuded arteries were not potentiated by repeated applications of the amino acid or by exposure of the strips for 24 hr to the bathing medium. Ca++ ionophore-induced contractions in the denuded strips were not potentiated by L-NA. Nicotine significantly increased the level of cyclic GMP in the arteries without endothelium; the increment was abolished by treatment with L-NA and hexamethonium. NO does not seem to be synthesized in smooth muscle in an amount sufficient to produce significant relaxation. It may be concluded that NO liberated from vasodilator nerves activates guanylate cyclase in smooth muscle and produces cyclic GMP, resulting in cerebroarterial relaxation.
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PMID:Role of nitric oxide in neurally induced cerebroarterial relaxation. 165 33

We analyzed mechanisms underlying neurogenic vasodilatation in dog and Japanese monkey renal arteries. Isometric mechanical responses of the arterial strip to nerve stimulation by nicotine were recorded. Nicotine-induced contractions were abolished by hexamethonium and potentiated by NG-nitro-L-arginine, a nitric oxide synthase inhibitor. The potentiating effect was reversed by L-arginine. NG-Nitro-L-arginine did not potentiate the contraction caused by norepinephrine. The nicotine-induced contraction was reversed to a relaxation by prazosin. The relaxation was not influenced by indomethacin, timolol, or atropine but was abolished by NG-nitro-L-arginine, methylene blue (a guanylate cyclase inhibitor), oxyhemoglobin (a nitric oxide scavenger), and hexamethonium. In the strips treated with NG-nitro-L-arginine, the nicotine-induced relaxation was restored by L-arginine. Histochemical study demonstrated perivascular nerves containing NADPH diaphorase and nitric oxide synthase immunoreactivity in dog and monkey arteries. We conclude that renal arteries are innervated by nitric oxide-mediated vasodilator and adrenergic vasoconstrictor nerves, and depression of the vasodilator nerve function by nitric oxide synthase inhibition potentiates the contraction caused by adrenergic nerve excitation.
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PMID:Nitroxidergic innervation in dog and monkey renal arteries. 773 21

1. Relaxations of strips of rat gastric fundus were elicited with nicotine (100 mumol/L), nitric oxide (NO; 30 mumol/L), sodium nitroprusside (SNP; 100 nmol/L) and vasoactive intestinal polypeptide (VIP; 1 nmol/L). 2. Methylene blue (30 mumol/L), an inhibitor of soluble guanylate cyclase, reduced relaxations elicited by NO and nicotine, but not those elicited by VIP. 3. Chymotrypsin (1 U/mL) abolished VIP-induced relaxations and reduced nicotine-induced relaxations, but had no effect on SNP-induced relaxations. 4. NG-nitro-L-arginine methyl ester (L-NAME; 100 mumol/L), an inhibitor of NO synthase, reduced relaxations elicited by nicotine, but not those elicited by SNP or VIP. 5. When nicotine-induced relaxations had been reduced by either L-NAME or chymotrypsin, the addition of the other agent produced a greater reduction. However, the relaxations were not abolished. 6. Nicotine-induced relaxations were abolished by tetrodotoxin (1 mumol/L) or hexamethonium (100 mumol/L), indicating that they were due to activation of neuronal nicotinic receptors. Their reduction by methylene blue and L-NAME indicates that an NO-like mediator was involved. Their reduction by chymotrypsin indicates that a VIP-like peptide was involved. However, since they were not abolished by a combination of L-NAME and chymotrypsin, it appears that at least one more as yet unidentified mediator may be involved.
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PMID:Mediators of nicotine-induced relaxations of the rat gastric fundus. 833 69

1. The NANC neuronal mechanisms for relaxations of the rat internal anal sphincter in response to electrical field stimulation (EFS) were studied in isolated preparations in the presence of atropine (1 microM), propranolol (3 microM) and phentolamine (3 microM). 2. EFS-induced relaxations were abolished by tetrodotoxin (1 microM) and reduced to 64% of control by the guanylate cyclase inhibitor ODQ (1 microM), but were not significantly reduced by the nitric oxide synthase inhibitor L-NAME (100 microM) or oxyhaemoglobin (10 microM). However, in the presence of tubocurarine (10 microM) or apamin (0.1 microM), L-NAME or oxyhaemoglobin greatly reduced or abolished EFS-induced relaxations. 3. The EFS-induced relaxations were mimicked by NO (10-100 microM) and by ATP (3-10 mM). The relaxations elicited by these agents were not affected by tetrodotoxin, L-NAME, tubocurarine or apamin. However, ATP-induced relaxations were reduced by the combination of L-NAME with tubocurarine or apamin. 4. Nicotine (10-100 microM) produced concentration-dependent relaxations that were abolished by tubocurarine (10 microM) or hexamethonium (200 microM). After desensitisation to nicotine (100 microM) and in its continued presence, the addition of L-NAME (100 microM) resulted in almost complete abolition of EFS-induced relaxations. 5. It is suggested that tubocurarine, hexamethonium and desensitisation to nicotine have an apamin-like action in the rat internal anal sphincter, the main effect being blockade of a purinergic component of the relaxant transmission process. 6. The findings suggest that both nitrergic and purinergic transmissions are involved in EFS-induced NANC relaxations of the rat internal anal sphincter, and there appears to be a complex interaction between these two pathways of transmission.
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PMID:Nitrergic and purinergic mechanisms and their interactions for relaxation of the rat internal anal sphincter. 1038 67

The underlying mechanisms of acetylcholine-induced intestinal relaxation in the lizard Liolaemus tenuis tenuis are still unknown. By using a classical model of intestinal recording of isometric contraction and relaxation in conjunction with specific pharmacological tools, this article studies the possible influence of EDRF/NO and nicotinic ganglionar receptors on the Ach-induced relaxation in an effort to elucidate the probable mechanisms involved in ACh effect. It was observed that the relaxation of the lizard intestine elicited by ACh (10(-7) - 4 x 10(-4) M) was not affected by hexametonium (5 x 10(-4) M) or tetrodotoxin (10(-6) M). Nicotine (10(-7) to 10(-4) M) induced relaxation was significantly antagonized by hexametonium; however, it was not influenced by tetrodotoxin. These results allow us to discard a neuronal pathway in cholinergic-induced relaxation, suggesting a more direct cholinergic effect on the smooth muscle, perhaps mediated by an unknown substance released by some specialized tissue. N-nitro-L-arginine, used to block NO-synthase and NO production, induced no changes in ACh-induced relaxation. Methylene blue, a soluble guanylate cyclase inhibitor, induced no changes in ACh-induced relaxation. These results allow us to discard a probable role of EDRF/nitric oxide in the ACh-induced relaxation of lizard small intestine, providing evidence that this mechanism could be different from that reported in other species.
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PMID:Effect of cholinergic agonists on muscular tonus of the lizard small intestine and esophagus. 1053 Mar 39

We investigated the mechanisms of contractile and relaxant responses to nerve stimulation by electrical pulses and nicotine in isolated monkey uterine artery strips denuded of the endothelium. In the strips contracted with prostaglandin F(2alpha), transmural electrical stimulation (5 Hz, 40 s) produced a contraction which was partially attenuated by prazosin and abolished or reversed to a relaxation by additional treatment with alpha,beta-methylene ATP. The relaxation was abolished by N(G)-nitro-L-arginine (L-NA) and restored by L-arginine but not by D-arginine. Atropine, D-NA, aminophylline and suramin, an inhibitor of P(2Y) purinoceptors, were without effect. The neurogenic relaxation was abolished by 1H-(1,2, 4)oxadiazolo(4,3)quinoxalin-1-one (ODQ), an inhibitor of soluble guanylate cyclase. Nicotine (10(-4) mol/l) elicited contraction or relaxation of uterine arteries; the contraction was reversed by combined treatment with prazosin and alpha,beta-methylene ATP. Nicotine-induced relaxations were abolished by L-NA and restored by L-arginine. The relaxation induced by exogenously applied NO (acidified NaNO(2) solution) was not influenced by L-NA but abolished by ODQ. It is concluded that contractions induced by nerve stimulation are mediated by norepinephrine and ATP liberated from sympathetic nerves that stimulate alpha(1)-adrenoceptors and P(2x) purinoceptors, respectively. The neurogenic relaxation seems to be mediated exclusively by nitric oxide synthesized from L-arginine in perivascular nerves that activates guanylate cyclase and produces cyclic GMP in smooth muscle.
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PMID:Mechanisms underlying contraction and relaxation induced by nerve stimulation in monkey uterine arteries. 1109 77

The neurotransmitters mediating relaxation of lower esophageal sphincter (LES) were studied using circular LES strips from adult pigs in organ baths. LES relaxation by sodium nitroprusside (1 nM-3 microM), vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP; 1 nM-1 microM), ATP (10 microM-30 mM), and tricarbonyldichlororuthenum dimer (1 microM-1 mM) was unaffected by tetrodotoxin (1 microM) or l-N(G)-nitroarginine methyl ester (l-NAME; 100 microM). Calcitonin gene-related peptide (CGRP; 1 nM-1 microM) did not affect LES tone. ATP relaxation was blocked by 1 microM apamin and the P2Y(1) antagonist MRS 2179 (N6-methyl 2'-deoxyadenosine 3',5'-bisphosphate; 10 microM). Apamin inhibited PACAP relaxation. VIP and PACAP relaxation was blocked by 10 U/ml alpha-chymotrypsin. L-NAME (-62.52 +/- 13.13%) and 1H-[1,2,4]oxadiazole-[4,3-alpha]quinoxalin-1-one (ODQ; 10 microM, -67.67 +/- 6.80%) similarly inhibited electrical LES relaxation, and apamin blocked non-nitrergic relaxation. Nicotine relaxation (100 microM) was inhibited by L-NAME (-60.37 +/- 10.8%) and ODQ (-41.90 +/- 7.89%), and apamin also blocked non-nitrergic relaxation. Non-nitrergic and apamin-sensitive LES relaxation by electrical stimulation or nicotine was strongly inhibited by MRS 2179, slightly inhibited by alpha-chymotrypsin and the P2X(1,2,3) receptor antagonist NF 279 (8,8 cent-[carbonylbis(imino-4,1-phenylenecarbonylimino-4,1-phenylenecarbonylimino)]bis-1,3,5-naphthalenetrisulfonic acid hexasodium salt; 10 microM), and unaffected by tin protoporphyrin IX (100 microM). Porcine LES relaxation after stimulation of intrinsic inhibitory motor neurons is mediated by two main neuromuscular pathways: nitric oxide through guanylate cyclase signaling and apamin-insensitive mechanisms and by non-nitrergic apamin-sensitive neurotransmission mainly mediated by ATP, ADP, or a related purine acting on P2Y1 receptors and a minor contribution of purinergic P2X1,2,3 receptors and PACAP. Nitrergic and purinergic co-transmitters show parallel effects of similar magnitude without major interplay. Our study shows no role for CGRP and only a minor one for VIP and carbon monoxide in porcine LES relaxation.
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PMID:Pharmacologic characterization of intrinsic mechanisms controlling tone and relaxation of porcine lower esophageal sphincter. 1630 17

Nicotine causes vasodilation in the renal vasculature through as yet unidentified mechanism. This study investigated the role of endothelial and non-endothelial factors in the vasodilatory action of nicotine in the rat isolated kidney. Nicotine vasodilation in phenylephrine-preconstricted perfused kidneys was evaluated in the absence and presence of drugs that interfere with nitric oxide synthase (NOS), K+ channels, cholinergic or adrenergic activity. Nicotine infusion (5 x 10(-5), 1 x 10(-4), and 5 x 10(-4) M) produced concentration-dependent decreases in the renal perfusion pressure, which continued for 20 min with a peak depressor effect observed at approximately 3 min. Nicotine vasodilation was associated with increases in norepinephrine and NO metabolites (nitrite/nitrate, NOx) levels in the renal effluent. Chemical denudation of the endothelium with 3-[(3-cholamidopropyl)-dimethyl-ammonio]-1-propane-sulfonate (CHAPS), or inhibition of NOS (NG-nitro-L-arginine, L-NNA), or guanylate cyclase (methylene blue) almost abolished the renal vasodilatory action of nicotine. Nicotine vasodilation was also significantly attenuated after selective blockade of ATP-sensitive (K(ATP), glibenclamide) or inward rectifier (Kir, BaCl2) K+ channels but remained unaltered after blockade of large-conductance calcium-activated (BKCa, tetraethylammonium, TEA) or voltage-dependent (Kv, 4-aminopyridine) K+ channels. Hexamethonium (ganglionic blocker), propranolol (beta-adrenceptor blocker), guanethidine (adrenergic neuron blocker), atropine (muscarinic antagonist) or the use of kidneys preconstricted with 80 mM KCl reduced the vasodepressor action of nicotine. Finally, exposure to diclophenac or neostigmine had no effect on nicotine vasodilation. Together, these findings implicate endothelial NOS and KATP and Kir channels in the renal vasodepressor effect of nicotine. Further, the sympathetic-dependent NO-mediated neurogenic vasodilation apparently contributes, at least partly, to nicotine vasodilation.
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PMID:Pharmacological characterization of cellular mechanisms of the renal vasodilatory effect of nicotine in rats. 1853 47

The presence of nitric oxide synthase (NOS) and role of nitric oxide (NO) in vascular regulation was investigated in the Australian lungfish, Neoceratodus forsteri. No evidence was found for NOS in the endothelium of large and small blood vessels following processing for NADPH-diaphorase histochemistry. However, both NADPH-diaphorase histochemistry and neural NOS immunohistochemistry demonstrated a sparse network of nitrergic nerves in the dorsal aorta, hepatic artery, and branchial arteries, but there were no nitrergic nerves in small blood vessels in tissues. In contrast, nitrergic nerves were found in non-vascular tissues of the lung, gut and kidney. Dual-wire myography was used to determine if NO signalling occurred in the branchial artery of N. forsteri. Both SNP and SIN-1 had no effect on the pre-constricted branchial artery, but the particulate guanylyl cyclase (GC) activator, C-type natriuretic peptide, always caused vasodilation. Nicotine mediated a dilation that was not inhibited by the soluble GC inhibitor, ODQ, or the NOS inhibitor, L-NNA, but was blocked by the cyclooxygenase inhibitor, indomethacin. These data suggest that NO control of the branchial artery is lacking, but that prostaglandins could be endothelial relaxing factors in the vasculature of lungfish.
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PMID:Vascular distribution of nitric oxide synthase and vasodilation in the Australian lungfish, Neoceratodus forsteri. 1869 49

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