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, PGF_1α, PGF_2α, 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 × 10^?7M, and 3 × 10^?7M, 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 β-adrenergic agonists (α, clonidine and 6-fluoronorepinephrine; β, 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 α- and β-adrenergic agonists with the AC system in cerebrovascular endothelium may play a role in the regulation of the cerebral microcirculation and/or blood pressure.