Functional and cellular interactions between nitric oxide and prostacyclin.
Nitric oxide (NO) and prostacyclin (PGI(2)) can be released by vascular agents to synergize their effects on vascular relaxation. In the present study we assess whether NO could affect PGI(2) production. We evaluated the effect of NO on PGI(2)-mediated arachidonic acid (AA)-induced relaxation in the perfused heart. We used cultured endothelial cells to characterize the mechanism involved in the NO effect on PGI(2) synthesis. AA-induced PGI(2) synthesis was enhanced when NO synthesis was inhibited. NO inhibited AA-induced relaxation and PGI(2) release in the coronary circulation. S-Nitroso-acetyl-DL-penicillamine (SNAP) decreased PGI(2) production in cultured endothelial cells. The SNAP effect was blunted by the inhibitor of soluble guanylate cyclase (LY-83,583) and the blocker of cGMP-dependent protein kinases (H-9). Specific cyclooxygenase-1 (COX-1) immunoprecipitation was associated to co-precipitation of four proteins. COX-1 showed neither serine nor threonine phosphorylation. One of the proteins that co-precipitated with COX-1 presented increased serine phosphorylation in the presence of SNAP. This effect was inhibited by the H-9. We suggest that NO, through cGMP-dependent protein kinases, produces the phosphorylation of a 104-kDa protein that is associated with inhibition in the activity of the COX-1, decreasing PGI(2) synthesis and thereby decreasing coronary PGI(2)-mediated vasodilatation.
Marcelín-Jiménez
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Department of Pharmacology and Toxicology, Centro de Investigación y de Estudios Avanzados del IPN, Avenida Instituto Politécnico Nacional 2508, c.p. 07300, Mexico City, Mexico.
Escalante
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D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D018929:Cell Culture Techniques; D003331:Coronary Vessels; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D051545:Cyclooxygenase 1; D004727:Endothelium / Q000166:cytology; D011464:Epoprostenol / Q000096:biosynthesis*; D006321:Heart / Q000502:physiology*; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000494:pharmacology*; D010766:Phosphorylation; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation
D007527:Isoenzymes; D008565:Membrane Proteins; D016718:Arachidonic Acid; D009569:Nitric Oxide; D011464:Epoprostenol; D051545:Cyclooxygenase 1; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; D017869:Cyclic GMP-Dependent Protein Kinases