Phorbol ester induces inhibition of arachidonate incorporation into phospholipids in human neutrophils.
PMA is known to enhance calcium ionophore A-23187 induced arachidonate release in human neutrophils. Mechanism of enhancement by PMA is not clear. We have found that neutrophils pretreated with PMA showed significant reduction in labeled arachidonate uptake. Decrease in arachidonate uptake following PMA treatment was attributed, at least in part, to inactivation of arachidonoyl CoA synthase and arachidonoyl CoA lysophosphatide acyltransferase, two key enzymes involved in arachidonate incorporation into phospholipids. These results suggest that PMA may induce protein kinase C activation which in turn may cause inactivation of the two enzymes involved in incorporation of arachidonate resulting in greater availability of arachidonate which is liberated by A-23187 for oxygenation and release into extracellular space.


BACKGROUND
PMA, 4 beta-phorbol 12-myristate 13-acetate; PDD, 4 alpha-phorbol 12,13-didecanoate; TXB2, thromboxane B2; LTB4, leukotriene B4; PC, phosphatidylcholine; LPC, lysophosphatidylcholine; DMSO, dimethylsulfoxide.
Yamazaki
H
H
Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Kentucky, Lexington 40536-0082.
Tai
H H
HH
D000217:Acyltransferases / Q000378:metabolism*; D001095:Arachidonic Acids / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D003066:Coenzyme A Ligases / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007975:Leukotriene B4 / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism*; D019301:Oleic Acid; D009829:Oleic Acids / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000378:metabolism
D001095:Arachidonic Acids; D009829:Oleic Acids; D010743:Phospholipids; D007975:Leukotriene B4; D019301:Oleic Acid; D000001:Calcimycin; D013929:Thromboxane B2; D000217:Acyltransferases; C065553:arachidonoyl coenzyme A lysophosphatide acyltransferase; D003066:Coenzyme A Ligases; C033896:arachidonate - CoA ligase; D013755:Tetradecanoylphorbol Acetate