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)

The purpose of this study was to examine and compare pulmonary vascular smooth muscle relaxation by clinically used agents as related to cGMP mediation (sodium nitroprusside, nitroglycerin) and cAMP mediation (isoproterenol, prostaglandin E1 (PGE1), and amrinone) in isolated rat pulmonary arterial rings. Isolated rat pulmonary arterial rings were suspended on a fine wire tensiometer in individual organ chambers. After confirming the endothelial integrity of the rings (response to acetylcholine), the rings were preconstricted with phenylephrine 10(-6) M. Dose-response curves for sodium nitroprusside, nitroglycerin, isoproterenol, amrinone, and PGE1 were then generated. Each of these agents was tested on six rings. Each ring was tested with each agent in a random order. The doses of sodium nitroprusside, isoproterenol, and nitroglycerin required to produce relaxation of isolated pulmonary arterial rings were not statistically different, but were significantly less than those required by amrinone and PGE1 (P < 0.05). These data suggest that relaxation of pulmonary vascular smooth muscle is more readily achieved via cGMP by guanylate cyclase activation (sodium nitroprusside, nitroglycerin) and via beta-adrenergic cAMP mediation (isoproterenol) than via cAMP-mediated pathways requiring either prostaglandin receptor activation (PGE1) or phosphodiesterase inhibition (amrinone).
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PMID:Pulmonary vascular smooth muscle relaxation by cGMP- versus cAMP-mediated mechanisms. 791 47

PGE(2), PGF(2alpha) and the thromboxane agonist U-46619 bind to bovine aortic endothelial cells and compete on the same binding site with similar affinity. In addition, binding remains unaffected by prolonged exposure to the ligand. These characteristics differ significantly from those of any known G-coupled prostaglandin receptor. Binding of PGE(2) to the cells is reduced in the presence of the cyclic nucleotides cGMP and cAMP, and is unaffected by protein kinase inhibitors. Removal of permeable cyclic nucleotides from the cell medium results in a fast and complete restoration of PGE(2) binding to the cells, suggesting that both cyclic nucleotides reduce PGE(2) binding by a reversible interaction with the prostaglandin-binding site, without the involvement of second messenger-activated protein kinases. Our data further show that binding of prostaglandins to bovine aortic endothelial cells is sensitive to heavy metals and to activators and blockers of calcium, ATP-sensitive K(+) and chloride channels. Nickel, a specific cyclic nucleotide-gated (CNG) channel activator, decreases PGE(2) binding and so do the CNG channel activators Rp-8-Br-PET-cGMPS and Sp-8-Br-PET-cGMPS. On the other hand, the calcium channel blockers pimozide, diltiazem as well as LY-83,583, a guanylate cyclase inhibitor, which were reported to block CNG channels, enhance PGE(2) binding. The sensitivity of PGE(2) binding to selective CNG channel modifying agents, as well as the rapid and reversible interaction with cyclic nucleotides, may suggest that the common low-affinity prostanoid-binding site on bovine aortic endothelial cells is associated with a molecular entity, which possess several properties of a CNG channel.
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PMID:Channel modulators affect PGE(2) binding to bovine aortic endothelial cells. 1198 95