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

[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.

[学科分类] 生物化学/生物物理

[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