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

This study investigates whether phorbol esters increase phosphoinositide hy drolysis in intact vascular smooth muscle, and the mechanism underlying the hydrolysis. Phorbol myristate acetate induced time- and concentration-depe ndent 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 indomethaci n, a cyclooxygenase inhibitor, but were only partially decreased by SQ29548 , a thromboxane A(2)/prostaglandin H-2 receptor antagonist. SQ29548 also on ly partially decreased elevated inositol monophosphate levels due to prosta glandin E-2, prostaglandin F-2 alpha, prostaglandin I-2 and carbacyclin, a stable prostaglandin I-2 analog. SQ29548 abolished elevated inositol monoph osphate levels due to U46619, a stable thromboxane A(2)/prostaglandin H-2 r eceptor agonist. These studies demonstrate that phorbol esters increase pho sphoinositide hydrolysis in intact vascular smooth muscle, and that the inc rease is due, at lease in part, to endogenously released prostaglandins oth er than prostaglandin H-2. (C) 2000 Elsevier Science Inc. All rights reserv ed.