Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.2 (guanylate cyclase)
 8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitric oxide is synthesized by constitutive oxide nitric synthase from the guanidine group of L-arginine. L-arginine, oxoborolidinone of L-arginine, nitrite and nitrate showed dose-dependent hypotensive effects after injection via the femoral vein in Wistar rats. The hypotensive effects were shifted to the right after treatment with methylene blue, which is a synthetic phenothiazine inhibitor of guanylate cyclase. Oxoborolidinone of L-arginine had high hypotensive effects with an effective half dose of 10 eta moles kg-1 and of mumoles kg-1 for methylene blue. Methylene blue also attenuated the toxic effects of all the tested compounds.
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PMID:[Toxicity and hypotensive effect of L-arginine oxoborolidinone and its modulation by methylene blue. Comparison with L-arginine, nitrite, and nitrate]. 1166 54

Platelet aggregation profiles were studied in chronic myelogenous leukemia patients who were undergoing hydroxyurea therapy. Nitric oxide (NO) generation induced by hydroxyurea was measured from the altered aggregatory response, in which the platelet suspension exhibits a de-aggregatory behaviour. NO caused platelet de-aggregation by generation of cyclic guanidine monophosphate through the activation of soluble guanylate cyclase (SGC). The fact that the observed response is specific to NO was confirmed by the reversal of the de-aggregatory behaviour in the presence of (1)H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), an inhibitor of SGC. Among the subjects studied, one subset showed an hydroxyurea-induced de-aggregatory effect that was inhibited by ODQ, whereas another subset did not show any such effect. The observed inter-individual variability in platelet aggregometric response after the ingestion of drugs may be an indicator for NO generation from hydroxyurea, and this may help to explain the drug efficacy encountered in such cases.
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PMID:Platelet aggregation profile as a marker of hydroxyurea bioavailability through nitric oxide generation in chronic myelogenous leukemia. 1669 May 34

Compound 48/80 (C48/80) is a synthetic condensation product of N-methyl-p-methoxyphenethylamine with formaldehyde and is an experimental drug used since the 1950s to induce anaphylactic shock through histamine release. This study was carried out to further elucidate the mechanism by which this drug induces nitric oxide (NO) release. Our specific goals were: (a) to verify if C48/80's relaxation occurs through the stimulation of histamine receptors; (b) to evaluate the endothelium-dependent relaxation induced by C48/80; (c) to identify NO as the endothelium-relaxing factor released by C48/80; (d) to identify the NO synthase (NOS) responsible for NO release; and (e) to verify if the relaxation induced by C48/80 is calcium and cyclic guanidine monophosphate (cGMP) dependent. Rabbit aorta segments, with and without endothelium, were suspended in organ chambers (25ml) filled with Krebs solution maintained at 37 degrees C, bubbled with 95% O(2)/5% CO(2) (pH 7.4). Phenylephrine was used to contract the segments. Other protocol drugs included H(1)- and H(2)-receptor antagonists, cyclooxygenase, NOS, guanylyl cyclase and phospholipase C (PLC) inhibitors. Endothelium-dependent relaxation induced by C48/80 was also studied in calcium-free Krebs solution associated with a calcium chelator. In summary, our investigation demonstrated that the C48/80 vasodilating action: (a) does not depend on H(1) and H(2) histamine receptors; (b) is NO endothelium-dependent; (c) is dependent on the endothelial constitutive NOS (NOS-3) isoform activation; (d) is cGMP-dependent; and that NOS-3 activation by C48/80: (a) is independent of PLC up to 25mug/ml and (b) is partially dependent of this lipase in higher doses.
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PMID:Compound 48/80 induces endothelium-dependent and histamine release-independent relaxation in rabbit aorta. 1807 32


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