Exogenous sn-1,2-diacylglycerols containing saturated fatty acids function as bioregulators of protein kinase C in human platelets.
The ability of exogenous sn-1,2-diacylglycerols and analogs to function as bioregulators of protein kinase C in human platelets was investigated. The activation of protein kinase C in platelets is indicated by specific phosphorylation of a 40,000-dalton protein. Dihexanoylglycerol, dioctanoylglycerol (diC8), didecanoylglycerol, and sn-1-oleoyl-2-acetylglycerol were active in stimulating 40,000-dalton protein phosphorylation. Only a trace of phosphorylation was elicited by dibutyrylglycerol. Phosphorylation was not induced by analogs of diC8 in which an -H, -SH, or -Cl group replaced the free -OH, nor by monoacylglycerols or long chain diacylglycerols. Maximum phosphorylation was induced by dihexanoylglycerol, diC8, and didecanoylglycerol at concentrations from 5 to 20 microM and between 5 and 30 S after exposure of platelets to these diacylglycerols. Under conditions of maximal phosphorylation of the 40,000-dalton protein, these diacylglycerols did not induce phosphatidylinositol turnover, or platelet aggregation, or stimulate release of ATP or serotonin. A small degree of aggregation was evident with platelets isolated in the absence of prostacyclin, and release of serotonin was observed when 1 mM Ca2+ or submaximal concentrations of ionophore A23187 were included. These results are consistent with a model in which platelet activation requires the simultaneous formation of two intracellular signals, diacylglycerols and Ca2+. These diacylglycerols and diacylglycerol analogs provide useful tools to investigate the function of diacylglycerols as bioregulators in intact cells.
Lapetina
E G
EG
Reep
B
B
Ganong
B R
BR
Bell
R M
RM
D001792:Blood Platelets / Q000201:enzymology*; D002118:Calcium / Q000494:pharmacology; D004075:Diglycerides / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005227:Fatty Acids / Q000494:pharmacology*; D005989:Glycerides / Q000494:pharmacology*; D006801:Humans; D010750:Phosphoproteins / Q000097:blood; D010766:Phosphorylation; D010974:Platelet Aggregation / Q000187:drug effects; D011493:Protein Kinase C; D011494:Protein Kinases / Q000378:metabolism*
D004075:Diglycerides; D005227:Fatty Acids; D005989:Glycerides; D010750:Phosphoproteins; C044295:1,2-dioctanoylglycerol; C044296:1,2-dihexanoylglycerol; C044297:1,2-didecanoylglycerol; C038237:1-oleoyl-2-acetylglycerol; D011494:Protein Kinases; D011493:Protein Kinase C; D002118:Calcium