Increased formation of phosphatidylinositol-4-phosphate in human platelets stimulated with lysophosphatidic acid.
Lysophosphatidic acid (LPA, 1-acyl-sn-glycerol 3-phosphate), at a concentration of 1-40 microM, was found to induce the formation of [3H]inositol-labelled phosphatidylinositol-4-phosphate (PIP) without significantly altering the levels of either phosphatidylinositol (PI) or phosphatidylinositol bisphosphate (PIP2) in washed human platelets. Preincubation of platelets with the cyclooxygenase/lipoxygenase inhibitor, BW755C at 100 microM, did not alter the LPA-induced formation of PIP. Activation of platelets with the phorbol ester, phorbol 12-myristate 13-acetate (PMA), elicited a similar response (induction of PIP formation). The specific protein kinase C (PKC) inhibitor, GF109203X (10 microM), completely blocked the effect of PMA but not the LPA-induced generation of PIP. The present results indicate that LPA can induce PIP formation via PI-4-kinase activation, through processes which are independent of the eicosanoid/TxA2 pathway and are not PKC-dependent.
Mani
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Department of Human Biology and Nutritional Sciences, University of Guelph, Ontario, Canada.
Gaudette
D C
DC
Holub
B J
BJ
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism*; D015777:Eicosanoids / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008246:Lysophospholipids / Q000494:pharmacology*; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000097:blood; D018129:Phosphatidylinositol Phosphates / Q000097:blood*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000097:blood; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013928:Thromboxane A2 / Q000097:blood
D015777:Eicosanoids; D004791:Enzyme Inhibitors; D016859:Lipoxygenase Inhibitors; D008246:Lysophospholipids; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; C037178:phosphatidylinositol 4-phosphate; D013928:Thromboxane A2; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate