Phorbol ester-induced phosphoinositide hydrolysis in rat aorta: Role of cyclooxygenase products

Abstract

This study investigates whether phorbol esters increase phosphoinositide hydrolysis in intact vascular smooth muscle, and the mechanism underlying the hydrolysis. Phorbol myristate acetate induced time- and concentration-dependent increases in phosphoinositide hydrolysis, as demonstrated by elevated inositol monophosphate levels, in deendothelialized rat aorta. The phorbol ester-elevated inositol monophosphate levels were abolished by indomethacin, a cyclooxygenase inhibitor, but were only partially decreased by SQ29548, a thromboxane A 2/prostaglandin H 2 receptor antagonist. SQ29548 also only partially decreased elevated inositol monophosphate levels due to prostaglandin E 2, prostaglandin F 2α, prostaglandin I 2 and carbacyclin, a stable prostaglandin I 2 analog. SQ29548 abolished elevated inositol monophosphate levels due to U46619, a stable thromboxane A 2/prostaglandin H 2 receptor agonist. These studies demonstrate that phorbol esters increase phosphoinositide hydrolysis in intact vascular smooth muscle, and that the increase is due, at lease in part, to endogenously released prostaglandins other than prostaglandin H 2.