PI 3-kinase and MAP kinase regulate bradykinin induced prostaglandin E(2) release in human pulmonary artery by modulating COX-2 activity.
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.
Division of Respiratory Medicine, University of Nottingham, City Hospital, Hucknall Road, Nottingham NG5 1PB, UK.
D A
DA
Bradbury
L
L
Corbett
A J
AJ
Knox
D016718:Arachidonic Acid / Q000378:metabolism; D001920:Bradykinin / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival; D002867:Chromones / Q000494:pharmacology; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007527:Isoenzymes / Q000187:drug effects / Q000378:metabolism*; D008565:Membrane Proteins; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D009025:Morpholines / Q000494:pharmacology; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000378:metabolism*; D011651:Pulmonary Artery / Q000166:cytology; D011725:Pyridines / Q000494:pharmacology; D011863:Radioimmunoassay; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors; D014316:Tritium; D048051:p38 Mitogen-Activated Protein Kinases
D002867:Chromones; D004791:Enzyme Inhibitors; D007093:Imidazoles; D007527:Isoenzymes; D008565:Membrane Proteins; D009025:Morpholines; D018377:Neurotransmitter Agents; D011725:Pyridines; D014316:Tritium; D016718:Arachidonic Acid; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D019869:Phosphatidylinositol 3-Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D010741:Phospholipases A; D015232:Dinoprostone; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole; D001920:Bradykinin; D013936:Thymidine