INCREASED FORMATION OF PHOSPHATIDYLINOSITOL-4-PHOSPHATE IN HUMAN PLATELETS STIMULATED WITH LYSOPHOSPHATIDIC ACID

Lysophosphatidic acid (LPA, 1-acyl-sn-glycerol 3-phosphate), at a conc entration of 1-40 mu M, was found to induce the formation of [H-3]inos itol-labelled phosphatidylinositol-4-phosphate (PIP) without significa ntly altering the levels of either phosphatidylinositol (PI) or phosph atidylinositol bisphosphate (PIP2) in washed human platelets. Preincub ation of platelets with the cyclooxygenase/lipoxygenase inhibitor, BW7 55C at 100 mu M, did not alter the LPA-induced formation of PIP. Activ ation of platelets with the phorbol ester, phorbol 12-myristate 13-ace tate (PMA), elicited a similar response (induction of PIP formation). The specific protein kinase C (PKC) inhibitor, GF109203X (10 mu M), co mpletely 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 o f the eicosanoid/TxA(2) pathway and are not PKC-dependent.