PROTEIN-KINASE-C REGULATION OF ATP-INDUCED PHOSPHOINOSITIDE HYDROLYSIS IN BOVINE AORTA ENDOTHELIAL-CELLS

This study investigated the mechanism of protein kinase C-mediated inh ibition of ATP-induced phospholipase C activation in cultured bovine a orta endothelial cells (BAEC). In BAEC labeled with H-3-inositol, phor bol myristate acetate (PMA) prevented ATP-induced inositol bisphosphat e and inositol trisphosphate formation. In membranes prepared from the se PMA-treated cells, Ca2+-, sodium fluoride,- GTP gamma S-, and ATP p lus GTP gamma S- stimulated inositol bisphosphate, but not inositol tr isphosphate, formation was inhibited. Inositol trisphosphate phosphata se activity was not altered in membranes from PMA-treated BAEC. These results suggest that 1) protein kinase C inhibits ATP-induced phosphol ipase C activation in BAEC through interference with the coupling of p hospholipase C with a G-protein and through an effect on phospholipase C itself and 2) different mechanisms are responsible for the inhibiti on by protein kinase C of the phospholipase C-mediated hydrolysis of p hosphatidylinositol bisphosphate and phosphatidylinositol phosphate.