PI 3-kinase and MAP kinase regulate bradykinin induced prostaglandin E 2 release in human pulmonary artery by modulating COX-2 activity

Abstract

Here we studied the role of phosphoinositide 3-kinase (PI 3-kinase) and mitogen activated protein (MAP) kinase in regulating bradykinin (BK) induced prostaglandin E 2 (PGE 2) production in human pulmonary artery smooth muscle cells (HPASMC). BK increased PGE 2 in a three step process involving phospholipase A 2 (PLA 2), cyclooxygenase (COX) and PGE synthase (PGES). BK stimulated PGE 2 release in cultured HPASMC was inhibited by the PI 3-kinase inhibitor LY294002 and the p38 MAP kinase inhibitor SB202190. The inhibitory mechanism used by LY294002 did not involve cytosolic PLA 2 activation or COX-1, COX-2 and PGES protein expression but rather a novel effect on COX enzymatic activity. SB202190 also inhibited COX activity.