PI 3-kinase and MAP kinase regulate bradykinin induced prostaglandin E(2) release in human pulmonary artery by modulating COX-2 activity |
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Authors: | Bradbury D A Corbett L Knox A J |
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Institution: | Division of Respiratory Medicine, University of Nottingham, City Hospital, Hucknall Road, Nottingham NG5 1PB, UK. |
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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 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. |
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Keywords: | Author Keywords: Bradykinin Cyclooxygenase Prostaglandin E2 Phosphoinositide 3-kinase Mitogen-activated protein kinase |
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