title: Phorbol myristate acetate stimulates formation of phosphatidyl inositol 4-phosphate and phosphatidyl inositol 4,5-bisphosphate in human platelets.
abstract: The tumor-promoting phorbol ester PMA increased the incorporation of 32P-phosphate into PIP (150%) and PIP2 (50%) in human platelets over the same range of concentrations that stimulate protein kinase C activity (i.e. 1-10 ng/ml). PMA also increased the total content of PIP (2.5-fold) and PIP2 (1.5-fold). The increase in 32P-PIP and 32P-PIP2 was 50% completed at 2 min after 10 ng/ml PMA, and was maximal by 20 min. The increase in PIP and PIP2 was accompanied by a fall of 32P-PI and PI mass over the same time period and concentration range of PMA, but no 32P-PA was formed, indicating that phosphoinositide hydrolysis by phospholipase C was not stimulated. Inhibition of phospholipase C activity by increasing platelet cyclic AMP did not duplicate the effects of PMA. We conclude that PMA may directly affect inositol lipid kinases and/or phosphatases, or that PMA stimulation of protein kinase C provides feedback regulation of the enzymes that determine the levels of polyphosphoinositides involved in transmembrane stimulus-response coupling.
mesh_terms: D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D010704:Phorbols / Q000494:pharmacology*; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols / Q000096:biosynthesis / Q000097:blood*; D011493:Protein Kinase C; D011494:Protein Kinases / Q000097:blood; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
chemical_list: D010704:Phorbols; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; C037178:phosphatidylinositol 4-phosphate; D011494:Protein Kinases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate