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)

In dog mesenteric vein strips, contractions induced by histamine relative to those induced by 5 mM Ba++ were potentiated by removal of endothelium. The induced contractions were potentiated by AA861, a lipoxygenase inhibitor, and methylene blue, a guanylate cyclase inhibitor, to an appreciably greater extent in the strips with endothelium than in those with damaged endothelium. Indomethacin did not potentiate the contraction induced by histamine. Cimetidine potentiated the contraction in control strips and those without endothelium to a similar extent whereas chlorpheniramine suppressed the contraction. Contractile responses to acetylcholine, norepinephrine, serotonin and prostaglandin (PG) F2 alpha were not potentiated by removal of endothelium. It may be concluded that histamine activates histaminergic receptors, possibly H1 but not H2, in endothelial cells and results in a release of vasodilator substance produced by lipoxygenase, which accumulates cellular cyclic GMP and relaxes mesenteric veins. The H1 and H2 receptors in smooth muscle cells appear to be responsible for contractions and relaxations, respectively. Acetylcholine, norepinephrine, serotonin and PGF2 alpha do not seem to release vasodilator substances from endothelium in an amount sufficient to cause significant relaxations of venous smooth muscle.
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PMID:Endothelium-dependent changes in the response to vasoconstrictor substances of isolated dog mesenteric veins. 287 60

The objective of the present investigation was to determine if gastrin at physiological concentrations has part of its mechanism(s) of action through stimulation of guanylate cyclase (EC 4.6.1.2). Human gastrin (I), pentagastrin, tetragastrin, and gastrin-related tetrapeptide all increased cyclic GMP levels and guanylate cyclase activity in rat gastric mucosa, whole stomach, and duodenum. Maximal stimulation was seen at 1 microM with all of the above. There was no further enhancement of guanylate cyclase with increasing the concentration to the millimolar range. The ED50 for human gastrin and pentagastrin was 0.01 microM, whereas the ED50 was 0.1 microM for tetragastrin and the tetrapeptide. No enhancement of guanylate cyclase activity was seen with decreasing the concentration to 1 nM of the respective gastrins. Cimetidine utilized at 1 microM or 1 mM concentrations partially blocked the augmentation by gastrin suggesting that part of this enhancement was through the histamine 2 receptor which has been shown to be important in pentagastrin-stimulated gastric acid release. Since the block was only partial these data would also indicate that some part of gastrin's activation of this enzyme is not mediated through the histamine 2 receptor.
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PMID:Cimetidine partially blocks gastrin's activation of gastric mucosal guanylate cyclase. 613 39