Prostacyclin inhibition of phosphatidic acid synthesis in human platelets is not mediated by protein kinase C.
The activation of protein kinase C in human platelets by phorbol-12, 13- dibutyrate (PDBu) results in the phosphorylation of a 40,000 dalton protein. This phosphorylation is time- and concentration-dependent. Maximal phosphorylation is rapid and is not affected by indomethacin or prostacyclin. PDBu does not promote activation of the phosphodiesteratic cleavage (phospholipase C) of the inositol phospholipids and the subsequent formation of 1,2-diacylglycerol or its phosphorylated product, phosphatidic acid. If platelets exposed to PDBu are subsequently stimulated with thrombin, this stimulus does not initiate further 40,000 dalton protein phosphorylation but will promote the formation of phosphatidic acid and also the phosphorylation of a 20,000 dalton protein (myosin light chain). However, prostacyclin will prevent the subsequent stimulation of phosphatidic acid synthesis by thrombin in a concentration-dependent manner. The fact that prostacyclin can affect the response to thrombin, even in the presence of phorbol ester, supports the idea that the enzymes related to the formation of phosphatidic acid or inhibition of its synthesis are not related to the phosphorylated 40K protein.
D001792:Blood Platelets / Q000201:enzymology*; D001798:Blood Proteins / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D011464:Epoprostenol / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000494:pharmacology; D010712:Phosphatidic Acids / Q000096:biosynthesis*; D010766:Phosphorylation; D010974:Platelet Aggregation / Q000187:drug effects; D011493:Protein Kinase C; D011494:Protein Kinases / Q000097:blood*; D013917:Thrombin / Q000494:pharmacology
D001798:Blood Proteins; D010703:Phorbol Esters; D010712:Phosphatidic Acids; D015240:Phorbol 12,13-Dibutyrate; D011464:Epoprostenol; D011494:Protein Kinases; D011493:Protein Kinase C; D013917:Thrombin