1-oleoyl-2-acetylglycerol and 1-2-didecanoylglycerol

These studies provide further support for the thesis that the activation of protein kinase C is likely involved in the prolactin (PRL) stimulation of mitogenesis in the Nb2 node lymphoma cell line. The diterpene mezerein is shown to potentiate the mitogenic effect of PRL at a hormone concentration which elicits a less than maximum response. A similar response was observed with two diglycerides, diolein and dicaprin. Neither mezerein nor the diglycerides affected the magnitude of response to a maximum stimulatory concentration of PRL.

Topics: Carcinogens; Cell Division; Diglycerides; Diterpenes; Drug Synergism; Enzyme Activation; Glycerides; Kinetics; Lymphoma; Prolactin; Protein Kinase C; Terpenes; Tumor Cells, Cultured

One of the most rapid actions of prolactin in mouse mammary gland explants is the stimulation of ornithine decarboxylase (ODC) activity. Several protein kinase C activators including mezerein, dicaprin, diolein, and 1-oleoyl-2-acetyl-rac-glycerol were found to stimulate ODC activity as does prolactin. Both mezerein and the diglycerides produced nonadditive responses when tested with maximum stimulatory concentrations of prolactin. The results of these studies therefore provide further evidence that the prolactin stimulation of ODC activation in the mammary gland may involve an activation of protein kinase C.

Topics: Animals; Diglycerides; Diterpenes; Female; Glycerides; Kinetics; Mammary Glands, Animal; Mice; Ornithine Decarboxylase; Pregnancy; Prolactin; Terpenes

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.

Topics: Blood Platelets; Calcium; Diglycerides; Enzyme Activation; Fatty Acids; Glycerides; Humans; Phosphoproteins; Phosphorylation; Platelet Aggregation; Protein Kinase C; Protein Kinases