Bradbury D A, Corbett L, Knox A J
Division of Respiratory Medicine, University of Nottingham, City Hospital, Hucknall Road, Nottingham NG5 1PB, UK.
FEBS Lett. 2004 Feb 27;560(1-3):30-4. doi: 10.1016/S0014-5793(04)00064-X.
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.
在此，我们研究了磷酸肌醇3激酶（PI 3激酶）和丝裂原活化蛋白（MAP）激酶在调节缓激肽（BK）诱导人肺动脉平滑肌细胞（HPASMC）产生前列腺素E2（PGE2）中的作用。BK通过涉及磷脂酶A2（PLA2）、环氧化酶（COX）和PGE合成酶（PGES）的三步过程增加PGE2。PI 3激酶抑制剂LY294002和p38 MAP激酶抑制剂SB202190抑制了BK刺激培养的HPASMC中PGE2的释放。LY294002的抑制机制不涉及胞质型PLA2激活或COX-1、COX-2和PGES蛋白表达，而是对COX酶活性的一种新作用。SB202190也抑制COX活性。
