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)

1. The activities of the enzymes involved in the metabolism of cyclic nucleotides were studied in sarcolemma prepared front guinea-pig heart ventricle; the enzyme activities reported here were linear under the assay conditions. 2. Adenylate cyclase was maximally activated by 3mM-NaF; NaF increased the Km for ATP (from 0.042 to 0.19 mM) but decreased the Ka for Mg2+ (from 2.33 to 0.9 mM). In the presence of saturating Mg2+ (15 mM), Mn2+ enhanced adenylate cyclase, whereas Co2+ was inhibitory. beta-Adrenergic amines (10-50 muM) stimulated adenylate cyclase (38+/-2%). When added to the assay mixture, guanyl nucleotides (GTP and its analogue, guanylyl imidophosphate) stimulated basal enzyme activity and enhanced the stimulation by isoproterenol. By contrast, preincubation of sarcolemma with guanylyl imidodiphosphate stimulated the formation of an 'activated' form of the enzyme, which did not reveal increased hormonal sensitivity. 3. The guanylate cyclase present in the membranes as well as in the Triton X-100-solubilized extract of membranes exhibited a Ka for Mn 2+ of 0.3 mM; Mn2+ in excess of GTP was required for maximal activity. Solubilized guanylate cyclase was activated by Mg2+ only in the presence of low Mn2+ concentrations; Ca2+ was inhibitory both in the absence and presence of low Mn2+. Acetylcholine as well as carbamolycholine stimulated membrane-bound guanylate cyclase. 4. Cylic nucleotide phosphodiesterase activities of sarcolemma exhibited both high-and low-Km forms with cyclic AMP and with cyclic GMP as substrate. Ca2+ ions increased the Vmax. of the cyclic GMP-dependent enzyme.
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PMID:Adenylate cyclase, guanylate cyclase and cyclic nucleotide phosphodiesterases of guinea-pig cardiac sarcolemma. 1 Aug 95

Guanylate cyclase activities were identified in a soluble fraction and a particular fraction obtained from the Arteria coronaria of cattle. The Km-value was 1.0 +/- 0.7 - 10(-4) M for the enzyme substrate complex of the guanylate cyclase of the soluble fraction and 9.2 +/- 1.5 - 10(-4) M for the particular fraction. For the enzyme activity of the soluble fraction Mn++ cannot be replaced by Ca++ or Mg++, whereas for the enzyme activity of the particulate fraction Mn++ can be replaced by Mg++ but not by Ca++. The guanylate cyclase of the particulate fraction can be activated by acetylcholine. This activation can be cancelled by atropine. Acetylcholine exerts no influence on the guanylate cyclase activity of the soluble fraction. ATP inhibits the enzyme activities of both fractions whereas cAMP shows no influence on the guanylate cyclase activity.
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PMID:[Proof of guanylate cyclase activity in the coronary artery of cattle]. 1 86

Exogenous cGMP can inhibit both basal and glucagon-stimulated production of glucose in liver slices from fed rats. Thus, cAMP and cGMP have opposite effects on the production of glucose in rat liver. Acetylcholine, an activator of guanylate cyclase (EC 4.6.1.2) in other systems, also inhibits the glucagon-stimulated production of glucose. No effect on glucose production was observed with secretin or exogenous GTP.
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PMID:Regulation of glucagon-stimulated production of glucose in rat liver by guanosine 3',5'-cyclic phosphate. 19 Nov 65

1. The signal transduction pathway for vasorelaxation induced by human alpha-calcitonin gene-related peptide (human alpha-CGRP) was studied in rat thoracic aortic rings preconstricted with noradrenaline (10(-7) M). 2. Vasorelaxation by human alpha-CGRP was inhibited by haemoglobin (10(-6) M) and methylene blue (10(-5) M) but was unaffected by ibuprofen (10(-5) M). 3. Acetylcholine caused a 16 fold increase in levels of guanosine 3':5'-cyclic monophosphate (cyclic GMP) with levels of adenosine 3':5'-cyclic monophosphate (cyclic AMP) being unaltered. Human alpha-CGRP caused a 12 fold increase in levels of cyclic GMP but, in contrast to acetylcholine, evoked a 2.5 fold rise in levels of cyclic AMP. The rises in cyclic nucleotides evoked by human alpha-CGRP and acetylcholine were dependent on the presence of an intact endothelium. 4. NG-nitro-L-arginine (L-NOARG: 10(-5) M), which inhibits nitric oxide synthetase, inhibited the relaxant response to human alpha-CGRP and cyclic GMP accumulation without affecting the cyclic AMP accumulation. 5. The data presented in this paper suggests that human alpha-CGRP relaxes the rat thoracic aorta by releasing nitric oxide and stimulating guanylate cyclase. The stimulation of adenylate cyclase by human alpha-CGRP probably precedes the activation of nitric oxide synthase but could be unrelated to the relaxant response.
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PMID:Human alpha-calcitonin gene-related peptide stimulates adenylate cyclase and guanylate cyclase and relaxes rat thoracic aorta by releasing nitric oxide. 136 70

Coculture of endothelial cells with atrial cells (R. A. Lew and A. J. Baertschi. Biochem. Biophys. Res. Commun. 163: 701-709, 1989) increased atrial natriuretic factor (ANF) release to 205 +/- 15% (n = 33 experiments) of basal secretion (2.02 +/- 0.33 ng/ml). Stimulation of ANF release by endothelial cells was significantly reduced (P < 0.05) by addition of the calcium channel antagonist nicardipine (Nic, 100 nM; by 69 +/- 4%), the guanylate cyclase activator sodium nitroprusside (SNP, 1 microM; by 97 +/- 27%), or acetylcholine (ACh, 10 microM; by 55 +/- 13%). Endothelial cell-conditioned medium elicited a 62 +/- 10% (n = 10) increase in ANF release. Rat and porcine endothelin (0.1-100 nM) each elicited a dose-dependent increase in ANF release [up to 84 +/- 14% (n = 18) over baseline]. The activity of conditioned medium was not affected by heat or trypsin treatment, but was significantly reduced by addition of Nic or SNP and was attenuated by ACh. Stimulation of ANF by 1 nM synthetic rat or porcine endothelin was also unaffected by heat or trypsin but was significantly reduced by Nic, SNP, and ACh. Addition of endothelin-specific antiserum abolished the ANF stimulatory activity of endothelial cell-conditioned medium. Neither inhibition of superoxide anion by superoxide dismutase nor inhibition of endothelium-derived nitric oxide production by NG-monomethyl-L-arginine affected the ANF release from coculture. Thus endothelial cells release a heat-stable, diffusible ANF stimulatory factor, which is not endothelium-derived relaxing factor or superoxide anion but is biologically and immunologically similar to endothelin.
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PMID:Endothelium-dependent ANF secretion in vitro. 141 54

Acetylcholine evokes the simultaneous release of endothelium-derived relaxing and contracting factors in aortas from spontaneously hypertensive rats. Only relaxing factors are released in aortas from normotensive controls. Experiments were designed to determine whether inhibitors of endothelium-dependent relaxations modify endothelium-dependent contractions. Rings of thoracic aortas of normotensive and spontaneously hypertensive rats, with and without endothelium, were suspended in organ chambers for isometric tension recording. Oxyhemoglobin (a scavenger of endothelium-derived relaxing factor) and NG-monomethyl L-arginine (an inhibitor of nitric oxide formation) augmented the contractions to acetylcholine. Methylene blue (an inhibitor of soluble guanylate cyclase) and superoxide dismutase (a scavenger of superoxide anions) did not modify these contractions. The contractions in the presence of oxyhemoglobin or NG-monomethyl L-arginine, like those in untreated rings, were endothelium-dependent; they only occurred in aortas from spontaneously hypertensive rats and were abolished by indomethacin. The contractions to acetylcholine in the presence of oxyhemoglobin were not affected by superoxide dismutase or deferoxamine. These data suggest that endothelium-derived relaxing factor inhibits endothelium-dependent contractions to acetylcholine in the spontaneously hypertensive rat aorta, probably by chemical inactivation of the endothelium-derived contracting factor rather than by stimulation of guanylate cyclase or scavenging of oxygen-derived free radicals.
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PMID:Nitric oxide inactivates endothelium-derived contracting factor in the rat aorta. 156 62

This experiment was designed to investigate whether chronic hypoxia affect rat pulmonary artery (PA) endothelium-dependent relaxation and the content of cGMP in PA. Both ACh and ATP could induce endothelium-dependent relaxation of PA, not prevented by indomethacin, but completely abolished by methylene blue. These results indicated that vasodilatation of PA induced by both ACh and ATP is mediated by EDRF (endothelium-derived relaxing factor). Chronic hypoxia significantly depressed PA endothelium-dependent relaxation. The percent relaxation of IPPA and EPPA by 10(-6) mol/L ACh was 61.3% and 59.2% of those in control, and the percent relaxation of IPPA and EPPA by 1.8 x 10(-5) mol/L ATP was 64.9% and 55.3% respectively of the control. Chronic hypoxia also depressed SNP-induced endothelium-independent relaxation. Chronic hypoxia significantly decreased the content of cGMP in PA. The basic level of cGMP was 51.9 +/- 5.7 (n = 14) in hypoxia group and 84.9 +/- 9.7 (n = 14) pmol/g wet wt. in control group (P less than 0.01). After treatment of PA with ACh (10(-7) mol/L), the content of cGMP was 91.4 +/- 7.3 (n = 5) pmol/g wet wt. in hypoxic group and 240.8 +/- 30.6 (n = 5) pmol/g wet wt. in control group (P less than 0.01). Our data suggest that chronic hypoxia might depress rat pulmonary artery endothelium-dependent relaxation through the inhibition of soluble guanylate cyclase in vascular smooth muscle cells.
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PMID:[Effect of chronic hypoxia on endothelium-dependent relaxation and the content of cGMP in rat pulmonary artery]. 164 78

It has been suggested that endothelin (ET) induces the release of endothelium-derived relaxing factor (EDRF). To explore the possible modification of ET-induced renal vasoconstriction by EDRF, we examined the effects of ET on renal vascular resistance (RVR) and urinary Na excretion (UNaV) in the rat isolated perfused kidney before and after the administration of EDRF antagonists. ET at 2 x 10(-11) to 2 x 10(-9) M elevated the RVR in a dose-dependent fashion, whereas it lowered the RVR at 10(-12) M. ET decreased UNaV significantly only at the highest dose. Acetylcholine at 10(-7) M decreased the RVR (-19%, p less than 0.05) and increased UNaV (+177%, p less than 0.05). In contrast, a soluble guanylate cyclase inhibitor, methylene blue (MB; 10(-5) M), increased the RVF by 30% (p less than 0.05) and decreased UNaV by 48% (p less than 0.05). Pretreatment with MB significantly augmented the ET-induced renal vasoconstriction by about 80%. However, UNaV was not influenced significantly. ET increased the urinary excretion of prostaglandin (PG) E2 and 6-keto-PGF1 alpha. Pretreatment with indomethacin (10(-5) M) also significantly enhanced the response of RVR to ET by 60% without changing UNaV. These results suggest that the vasoconstrictor, but not the antinatriuretic, activity of ET may be modified by the release of EDRF and prostacyclin.
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PMID:Role of endothelium-derived relaxing factor in endothelin-induced renal vasoconstriction. 172 20

A role for altered endothelial cell function is emerging in the pathogenesis of disease. We have previously demonstrated that Dirofilaria immitis, the canine heartworm, depresses endothelium-dependent responses and alters the mechanism of relaxation in the in vivo femoral artery of infected dogs. Exposure of rat aorta to the parasite or parasite-conditioned medium selectively depresses endothelium-dependent relaxation. D. immitis is closely related to the major human filarial pathogens. This study was designed to examine the effect of chronic infection with the filarial nematode Brugia pahangi on endothelium-mediated responses of the rat aorta in vitro. We tested the hypothesis that endothelium-dependent responses are depressed in the aorta from rats infected with B. pahangi. Rings of thoracic and abdominal aorta were suspended in muscle baths for measurement of isometric tension. Dose-response relations to norepinephrine, endothelium-dependent dilators (acetylcholine, histamine, and A23187), and nitroglycerin were done. In some experiments, inhibitors of cyclooxygenase (indomethacin and aspirin), guanylate cyclase (methylene blue), and nitric oxide formation (N-nitro-L-arginine methyl ester; L-NOARG) were used. No differences in vascular reactivity were detected in the thoracic aorta. In contrast, endothelium-dependent responses in abdominal aorta of Brugia-infected rats were significantly depressed when compared with control aorta from noninfected rats. Acetylcholine relaxation was further depressed by indomethacin and aspirin. After L-NOARG, acetylcholine relaxation in control abdominal aorta was completely abolished; however, in abdominal aorta of Brugia-infected rats, acetylcholine still caused relaxation. Methylene blue inhibited acetylcholine relaxation in both control and Brugia-infected abdominal aorta; however, relaxation in Brugia-infected aorta was significantly greater than control. This study demonstrates that endothelium-dependent relaxation can be altered by chronic experimental filarial infection in the absence of direct contact between the blood vessel and the parasite. The mechanism of relaxation in the Brugia-infected abdominal aorta appears to be altered when compared with control, suggesting that parasites are capable of modulating vascular reactivity by inducing changes in endothelial cell behavior. The mechanism may involve parasite-induced local inflammation or alterations in endothelial cell metabolism. Understanding how chronic experimental filarial infection alters vascular reactivity may enhance our understanding of the pathogenesis of human filariasis.
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PMID:Depression of endothelium-dependent relaxation in aorta from rats with Brugia pahangi lymphatic filariasis. 190 79

The role of the endothelium as a participant in the responses to vasoactive agents was evaluated in isolated canine hepatic artery (HA) and portal vein (PV) rings. Endothelial and smooth muscle integrity was determined by pharmacologic responses as well as by histologic examination. Smooth muscle relaxation was expressed as the percent of decrease of norepinephrine-induced isometric contraction. Acetylcholine (ACh)-induced relaxation of the HA was abolished by removing the endothelium or by the addition of either hemoglobin, methylene blue (MB) or Ng-mono-methyl-L-arginine. In addition, relaxation induced by nitroglycerin, but not that induced by prostaglandin E1, was attenuated by MB. These data suggest endothelium-dependency of the relaxation to ACh and mediation of the response by endothelium-derived relaxing factor through activation of guanylate cyclase. In contrast, ACh produced contraction of the PV which was unaffected by removing the endothelium. The calcium ionophore, A23187, on the other hand, produced relaxation of the PV, which was significantly decreased by removing the endothelium. Relaxation of both HA and PV, produced by 2-chloroadenosine (2-C-Ado) was partially attenuated by removing the endothelium. With the endothelium intact, neither hemoglobin, MB, Ng-monomethyl-L-arginine nor indomethacin affected the responses to 2-C-Ado in the HA and PV, suggesting that the responses were not mediated by endothelium-derived relaxing factor or products of guanylate cyclase or cyclooxygenase activity. Nitroglycerin relaxed both vessels in the presence or absence of endothelium, indicating that removal of the endothelium had not affected smooth muscle function.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of endothelium in responses of isolated hepatic vessels to vasoactive agents. 192 Jan 37


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