Prostacyclin and β-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) block calcium ionophore-induced PGI2 production by 62%. The addition of 3 mM dibutyryl cyclic AMP, along with IBMX, increases the inhibition to 96%. Release of 3H-arachidonate from membrane phospholipids was inhibited 21% by dibutyryl cyclic AMP, 48% by IBMX, and 76% by isoproterenol plus IBMX. Inhibition by isoproterenol was reversed by 10 μM propranolol. Release of 3H-arachidonate was also reduced 75% by a combination of 10μM 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.