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

FEBS Letters

Corbett, L¹  Bradbury, D.A¹  Knox, A.J¹ 

[1] Division of Respiratory Medicine, University of Nottingham, City Hospital, Hucknall Road, Nottingham NG5 1PB, UK

关键词: Bradykinin;    Cyclooxygenase;    Prostaglandin E2;    Phosphoinositide 3-kinase;    Mitogen-activated protein kinase;    AA;    arachidonic acid;    BK;    bradykinin;    COX;    cyclooxygenase;    cPLA2;    cytosolic phospholipase A2;    DMSO;    dimethyl sulphoxide;    HPASMC;    human pulmonary artery smooth muscle cells;    LY294002;    [2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one];    MAP kinase;    mitogen activated protein kinase;    PI 3-K;    phosphoinositide 3-kinase;    PG;    prostaglandin;    SB202190 [4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)1H-imidazole;   

DOI  :  10.1016/S0014-5793(04)00064-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 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 E₂ (PGE₂) production in human pulmonary artery smooth muscle cells (HPASMC). BK increased PGE₂ in a three step process involving phospholipase A₂ (PLA₂), cyclooxygenase (COX) and PGE synthase (PGES). BK stimulated PGE₂ 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 PLA₂ activation or COX-1, COX-2 and PGES protein expression but rather a novel effect on COX enzymatic activity. SB202190 also inhibited COX activity.

【 授权许可】

Unknown