Cerebral endothelial cell culture. II. Adenylate cyclase response to prostaglandins and their interaction with the adrenergic system.

The response of endothelial adenylate cyclase (AC) to prostaglandins (PGE1, PGE2, PGF1 alpha, PGF2 alpha, PGD2 and PGI2) and the relationship of PGE2 to adrenergic systems were investigated in cerebrovascular endothelial cultures. E-type prostaglandins and PGI2 were more effective in stimulating endothelial AC (EC50 = 3 x 10(-7)M, and 3 x 10(-6)M, respectively) than prostaglandins of the F-series and PGD2 which activated AC at high doses only. A modulation of endothelial AC response to either PGE2 or norepinephrine (NE) was observed in the presence of both agents in the system. It was manifested by a dose-dependent NE inhibition of the PGE2-stimulated formation of cAMP, which was partially restored by phentolamine. Alpha and beta-adrenergic agonists (alpha, clonidine and 6-fluoronorepinephrine; beta, isoproterenol) also partly blocked while forskolin and PGE2 synergistically stimulated the production of cAMP in the endothelial cultures. These findings strongly suggest that the interaction of prostaglandins and alpha- and beta-adrenergic agonists with the AC system in cerebrovascular endothelium may play a role in the regulation of the cerebral microcirculation and/or blood pressure.