title: Prostacyclin and beta-adrenergic catecholamines inhibit arachidonate release and PGI2 synthesis by vascular endothelium.
abstract: We have investigated the mechanism by which cyclic AMP inhibits PGI2 synthesis in cultured bovine aortic endothelial cells. Inhibition of cyclic AMP phosphodiesterase activity by 3-isobutyl-1-methylxanthine (IBMX) blocks calcium ionophore-induced PGI2 production by 62%. The addition of 3 mM dibutyryl cyclic AMP, alone with IBMX, increases the inhibition to 96%. Release o 3H-arachidonate from membrane phospholipids was inhibited 25% by dibutyryl cyclic AMP, 48% by IBMX, and 76% by isoproterenol plus IBMX. Inhibition by isoproterenol was reversed by 10 micro M propranolol. Release of 3H-arachidonate was also reduced 75% by a combination of 10 micro M PGI2 and 3 mM IBMX. We conclude that hormones like isoproterenol and PGI2 may regulate endothelial cell PGI2 biosynthesis by increasing intracellular cyclic AMP, which then inhibits release of endogenous arachidonate from membrane phospholipids.
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015121:6-Ketoprostaglandin F1 alpha; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic; D001095:Arachidonic Acids / Q000378:metabolism*; D001241:Aspirin / Q000494:pharmacology; D002395:Catecholamines / Q000494:pharmacology*; D002417:Cattle; D004727:Endothelium / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis / Q000494:pharmacology*; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology*; D011460:Prostaglandins F / Q000096:biosynthesis
chemical_list: D000318:Adrenergic beta-Agonists; D001095:Arachidonic Acids; D002395:Catecholamines; D011453:Prostaglandins; D011460:Prostaglandins F; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D015121:6-Ketoprostaglandin F1 alpha; D005707:Gallic Acid; D011433:Propranolol; D011464:Epoprostenol; D007545:Isoproterenol; D001241:Aspirin; D015056:1-Methyl-3-isobutylxanthine