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)

The present study was carried out to evaluate the effects of biologically active atriopeptin II (APII) in synchronously contracting monolayer cultures of rat ventricular myocytes. The effects of 10 nM APII on Ca influx, contractile behavior and cyclic nucleotide content of the cells were measured. Applied acutely APII had no effect on Ca influx. There was however a time-dependent effect such that after 30 min Ca influx (pmol/cm2/s) had declined from a control (mean +/- S.E.M.) of 1.53 +/- 0.16 to 1.02 +/- 0.07 (P less than 0.001; n = 6). There was parallel decline in both the magnitude and velocity of cell edge motion which was maximal in 30 min at which time cell edge motion measured 65.3 +/- 4.4% of control. Treatment with APII for 30 min decreased cAMP (pmol/mg protein) from 5.35 +/- 0.17 to 2.86 +/- 0.24 (P less than 0.001; n = 5). At the same time cGMP (pmol/mg protein) increased from 0.86 +/- 0.21 to 2.14 +/- 0.33 (P less than 0.001; n = 5). Further studies elucidated the fact that the decline in Ca influx and contractile behavior was dependent on the decrease in cAMP rather than the increase in cGMP. Pre-treatment of the cells with 5 ng/ml of pertussis toxin to ADP-ribosylate the Gi protein abolished the effects of APII on cAMP, Ca influx and contractile behavior. The results indicate that in myocardial cells, as in other cells, APII stimulates guanylate cyclase and inhibits adenylate cyclase. The resultant fall in cAMP decreases Ca influx and negatively influences the contractile behavior of the cells.
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PMID:Effect of atriopeptin II on Ca influx, contractile behavior and cyclic nucleotide content of cultured neonatal rat myocardial cells. 196 67

The activity of human platelet guanylate cyclase, and the activation of the enzyme by sodium nitroprusside were decreased in platelets with increased aggregability; these platelets were obtained from diabetes mellitus patients. Anomalies in guanylate cyclase activity and ADP-induced aggregation were more pronounced in platelets from subjects with type II than those with type I diabetes.
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PMID:Guanylate cyclase in human platelets with different aggregability. 197 57

ATP has been reported to increase basal and atrial natriuretic factor (ANF)-stimulated guanylate cyclase activity. The structural features of ATP involved in the activation of guanylate cyclase were examined by employing a variety of ATP analogs with modification either at the phosphate chain or at the ribose moiety. Among the natural adenine nucleotides, ATP and ADP were able to increase both basal and ANF-stimulated guanylate cyclase activities in rat lung membranes. AMP had no effect. ATP was more effective than AMPPCP (the non-hydrolyzable analog of ATP), and ADP was more effective than ADP beta S and AMPCP (the hydrolysis-resistant analogs of ADP) to increase basal and ANF-stimulated guanylate cyclase activities. Removal of the oxygen atom from the ribose moiety of ATP or ADP significantly reduced their potency. Thus, the length of the phosphate chain and the hydroxyl groups at the ribose moiety are both determinants for nucleotide mediated guanylate cyclase activation.
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PMID:Structural requirements of ATP for activation of basal and atrial natriuretic factor-stimulated guanylate cyclase in rat lung membranes. 198 Jun 48

The effect of N-(omega-aminoalkyl) derivatives of naphthalene-1-sulfamide on the activity of soluble guanylate cyclase and on human platelet aggregation at the first (reversible) step of the guanylate cyclase reaction was studied. Low (approximately 10(-7)-10(-6) M) concentrations of the above compounds were shown to stimulate the guanylate cyclase activity; some derivatives caused simultaneous inhibition of platelet aggregation induced by ADP. Some fragments of the chemical structure of the molecules responsible for the enzyme activity regulation in the tested systems were identified. The naphthalene-1-sulfamide derivatives carrying 6-aminohexyl or 8-amino-octyl groups of the sulfamide substituent as well as chlorine atom at positions 4 or 5 of the naphthalene ring appeared to be the most potent activators of platelet guanylate cyclase and inhibitors of platelet aggregation at the reversible step of the enzymatic reaction.
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PMID:[Effect of N-(6-aminohexyl)-5-chloronaphthalene-1-sulfamide (W-7) and its analogs on the activity of soluble guanylate cyclase and on human platelet aggregation]. 198 51

1. The effects of bradykinin, adenosine diphosphate, calcium ionophore A23187 and nitric oxide on the production of adenosine 3':5'-cyclic monophosphate (cyclic AMP) and guanosine 3':5'-cyclic monophosphate (cyclic GMP) were investigated in cultured aortic endothelial cells of the pig. 2. Bradykinin (10(-7) M), adenosine diphosphate (3 x 10(-5) M), nitric oxide (2 x 10(-6) M) and A23187 (10(-6) M) stimulated the production of cyclic GMP. This stimulation reached a maximum within 1 min and declined rapidly with the first three agonists whereas that induced by A23187 was long-lasting. 3. These concentrations of bradykinin, A23187 and nitric oxide had no effect on cyclic AMP production. However, adenosine diphosphate (3 x 10(-5) M) slightly but significantly enhanced its production by about 1.7 fold. 4. The basal content of cyclic GMP in endothelial cells was significantly reduced by haemoglobin (10(-5) M, a scavenger of endothelium-derived relaxing factor(s] and methylene blue (10(-5) M, an inhibitor of the activation of soluble guanylate cyclase) and was significantly enhanced by superoxide dismutase (500 u ml-1, a scavenger of superoxide anions). The basal content of cyclic GMP was not affected by NG-monomethyl-L-arginine (10(-5) M, a specific inhibitor of the formation of nitric oxide from L-arginine) and was slightly but significantly increased by its D-enantiomer, NG-monomethyl-D-arginine. 5. The production of cyclic GMP stimulated by bradykinin, adenosine diphosphate, A23187 and nitric oxide was inhibited by haemoglobin (10 5M) and methylene blue (10- M) but was unaffected by superoxide dismutase (500 u ml 1)- 6. The production of cyclic GMP stimulated by bradykinin, adenosine diphosphate or A23187, but not that stimulated by nitric oxide, was significantly reduced by N0-monomethyl-L-arginine (10-M). The production of cyclic GMP evoked by nitric oxide, but not that induced by the other three agents, was enhanced significantly by N0-monomethyl-D-arginine by about 1.5 fold. 7. These data indicate that the endothelium-dependent vasodilators bradykinin, adenosine diphosphate and A23187 activate the production of cyclic GMP in endothelial cells via the synthesis of nitric oxide, which in turn stimulates the soluble guanylate cyclase.
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PMID:Stimulation of cyclic GMP production in cultured endothelial cells of the pig by bradykinin, adenosine diphosphate, calcium ionophore A23187 and nitric oxide. 217 13

Dilution of thrombocyte-rich blood plasma (down to 2.5 x 10(8) thrombocytes/ml) enabled to avoid an irreversible phase of the ADP-induced thrombocyte aggregation; the reversible phase of aggregation was followed by deaggregation. The reversible aggregation of thrombocytes was studied in healthy persons and patients with diabetes mellitus within wide ranges of ADP concentrations (including 10 microM) using the diluted blood plasma. Thrombocytes of the patients with diabetes mellitus of the I and II types were found to be 1.6- and 2.33-fold more sensitive to the ADP aggregating effect as compared with thrombocytes of healthy persons. The elevated rate of thrombocytes aggregation in diabetes mellitus appears to be related to early decrease in activity of thrombocyte guanylate cyclase and to its ability to be activated.
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PMID:[ADP-induced aggregation of human platelets in diabetes mellitus]. 223 25

The author reviews the problem of the pattern of lipid peroxidation in cancer cells with special reference to a comparison between normal liver cells and hepatomas both transplanted and induced by diethylnitrosamine. It is stated that the loss of lipid peroxidation is proportional to the degree of de-differentiation of hepatoma cells. During carcinogenesis, however, the loss is already evident at the stage of preneoplastic nodules. A common feature of all tumors, independently of the extent of the loss of peroxidation in basal conditions, is the lack of further stimulation by ADP/iron or by ascorbate/iron. As regards the reasons for the decline in lipid peroxidation, they are certainly not unique. An important cause is the low activity of the enzymes of the monooxygenase microsomal chain. Another very important one is the change in lipid composition of membranes, with a marked decrease in polyunsaturated fatty acids, which are the main substrate for lipid peroxidation. It has been shown that enrichment of membranes of hepatomas with arachidonic acid results in restoration of stimulation of peroxidation by ascorbate/iron, but not with ADP/iron. The last type of stimulation mostly reflects the behaviour of the monooxygenase chain, whereas ascorbate/iron-induced stimulation does not require the presence of an efficient cytochrome P450-chain. Another cause for decreased lipid peroxidation in tumors is the increased rigidity of membranes, due to the large increase in cholesterol content: this prevents to some extent the influx of oxygen inside the membranes. Yet another cause is the presence of increased amounts of antioxidants in both cytosol and membranes. The main toxic product of lipid peroxidation, 4-hydroxynonenal, has been found to elicit several actions at extremely low concentrations. In fact, 4-hydroxynonenal stimulates chemotaxis of polymorphonuclear leukocytes, stimulates plasma membrane adenylate cyclase, stimulates plasma membrane guanylate cyclase, and stimulates phospholipase C. The last three enzymes involve the action of G-proteins. The effect of the aldehyde is present at less than micromolar concentrations, which may occur inside the cells in certain conditions. Moreover, at concentrations from 10(-6) to 10(-7) M, the aldehyde is able to block oncogene c-myc expression in the human erythroleukemic K562 cell line, which at the same time becomes able to express the gamma-globin gene. These facts are discussed with reference to a possible biological meaning of the loss of lipid peroxidation in tumors.
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PMID:Lipid peroxidation and cancer: a critical reconsideration. 251 Mar 83

Changes in viscous drag acting upon the endothelial lining and a number of circulating agonists (ATP, ADP, serotonin, thrombin) stimulate the release of EDRF from intact endothelial cells. EDRF is probably identical with nitric oxide (NO), the vasoactive compound which is also formed in the metabolism of nitrovasodilators in the vasculature (some of them directly release NO without the essential foregoing bioconversion step). Albuminally released NO stimulates soluble guanylate cyclase (sGC) in the vasculature initiating vasodilation; luminally released NO stimulates, sGC in platelets and increases cyclic GMP inhibiting platelet activation and aggregation. Endothelial impairment brings about loss of dilator and antiaggregant capacity.
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PMID:[Inhibition of thrombocyte aggregation and adhesion by endothelium-derived relaxant factor (EDRF) and their pathophysiologic significance]. 251 72

Dietary supplementation with cod-liver oil significantly augments endothelium-dependent relaxations in porcine coronary arteries. The present study was designed to examine the effect of dietary administration of omega 3 polyunsaturated fatty acids (mainly eicosapentaenoic acid, the major component of fish oil) on endothelium-dependent relaxations in porcine coronary arteries. Male Yorkshire pigs were maintained 4 wk on a regular diet with or without supplementation with purified eicosapentaenoic acid (3.5 g/day) and docosahexaenoic acid (1.5 g/day). Endothelium-dependent relaxations were examined in vitro. In rings from the treated group, endothelium-dependent relaxations were augmented in response to bradykinin, serotonin, and ADP, but not to the calcium ionophore A23187. These augmentations were not altered by indomethacin but were significantly inhibited by methylene blue, an inhibitor of guanylate cyclase. In the treated group, endothelium-dependent relaxations to aggregating platelets also were significantly augmented; platelet-induced contractions of quiescent rings were inhibited more by the presence of the endothelium than in arteries from the control group. Bioassay experiments demonstrated that the release of endothelium-derived relaxing factor(s) by bradykinin and relaxations of the vascular smooth muscle to the factor(s) were greater in arteries from the treated group. These observations indicate that dietary omega 3 polyunsaturated fatty acids augment receptor-operated endothelium-dependent relaxations, partly due to the augmented release of endothelium-derived relaxing factor(s) and partly due to the augmented relaxation of the vascular smooth muscle to the factor(s).
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PMID:Dietary omega 3 fatty acids and endothelium-dependent relaxations in porcine coronary arteries. 253 56

The objective of this study was to characterize the role of membrane potential and cyclic nucleotides in endothelium-dependent dilation of cerebral arteries. Middle cerebral arteries isolated from cats were depolarized and constricted in response to serotonin or when subjected to transmural pressures greater than 50 mm Hg. Acetylcholine (ACh) and ADP caused vasodilation and a sustained, dose-dependent hyperpolarization of up to 20 mV in this artery. The membrane potential change preceded the vasodilation by approximately 6 s. Hyperpolarizations and dilations to ACh and ADP did not occur in preparations without endothelium. The hyperpolarizations were abolished by ouabain (10(-5) M), which also blocked the dilator response to ACh. However, dilations to ADP were unaffected by ouabain. Methylene blue (5 x 10(-5) M), a guanylate cyclase inhibitor, had no effect on the responses to ACh or ADP in the presence or absence of ouabain. Cyclic guanosine monophosphate (cGMP) levels were not altered in cerebral arteries exposed to ACh or ADP. However, ADP did increase cyclic adenosine monophosphate levels in these blood vessels. We conclude that although membrane hyperpolarizations may be adequate to cause vasodilation, at least one other pathway of endothelium-dependent vasodilation also is present in feline cerebral arteries. Cyclic GMP does not appear to be involved in this alternate pathway of dilation.
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PMID:Endothelium-dependent dilation of feline cerebral arteries: role of membrane potential and cyclic nucleotides. 254 Nov 45


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