Protein kinase C regulation of ATP-induced phosphoinositide hydrolysis in bovine aorta endothelial cells.
This study investigated the mechanism of protein kinase C-mediated inhibition of ATP-induced phospholipase C activation in cultured bovine aorta endothelial cells (BAEC). In BAEC labeled with 3H-inositol, phorbol myristate acetate (PMA) prevented ATP-induced inositol bisphosphate and inositol trisphosphate formation. In membranes prepared from these PMA-treated cells, Ca(2+)-, sodium fluoride-, GTP gamma S-, and ATP plus GTP gamma S-stimulated inositol bisphosphate, but not inositol trisphosphate, formation was inhibited. Inositol trisphosphate phosphatase activity was not altered in membranes from PMA-treated BAEC. These results suggest that 1) protein kinase C inhibits ATP-induced phospholipase C activation in BAEC through interference with the coupling of phospholipase C with a G-protein and through an effect on phospholipase C itself, and 2) different mechanisms are responsible for the inhibition by protein kinase C of the phospholipase C-mediated hydrolysis of phosphatidylinositol bisphosphate and phosphatidyl-inositol phosphate.
Chuprun
J K
JK
Department of Pharmacology and Cell Biophysics, University of Cincinnati, College of Medicine, Ohio 45267-0575, USA.
Rapoport
R M
RM
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006868:Hydrolysis; D000072181:Inositol Polyphosphate 5-Phosphatases; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D011493:Protein Kinase C / Q000502:physiology*; D012969:Sodium Fluoride / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism
D010716:Phosphatidylinositols; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D000255:Adenosine Triphosphate; D012969:Sodium Fluoride; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases; D010738:Type C Phospholipases; D013755:Tetradecanoylphorbol Acetate