PI 3-kinase and MAP kinase regulate bradykinin induced prostaglandin E2 release in human pulmonary artery by modulating COX-2 activity

被引:20
作者
Bradbury, DA [1 ]
Corbett, L [1 ]
Knox, AJ [1 ]
机构
[1] Univ Nottingham, City Hosp, Div Resp Med, Nottingham NG5 1PB, England
来源
FEBS LETTERS | 2004年 / 560卷 / 1-3期
关键词
bradykinin; cyclooxygenase; prostaglandin E-2; phosphoinositide; 3-kinase; mitogen-activated protein kinase;
D O I
10.1016/S0014-5793(04)00064-X
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:30 / 34
页数:5
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