Diacylglycerol causes Ca release from the platelet dense tubular system: comparisons with Ca release caused by inositol 1,4,5-triphosphate.
Platelet activation is often associated with an increase in the cytosolic free Ca concentration that is due in part to Ca release from the dense tubular system. The present studies examine whether the diacylglycerol formed by phosphoinositide hydrolysis during platelet activation contributes to this process. The effect of diacylglycerol on the dense tubular system was tested using platelets that were permeabilized with saponin and then allowed to accumulate 45Ca. A synthetic diacylglycerol, 1-oleoyl-2-acetoyl glycerol (OAG), released up to 70% of the ionophore A23187-releasable 45Ca, a fraction identical to that discharged by inositol 1,4,5-triphosphate (IP3) under the same conditions. 45Ca release was half-maximal at 40 microM OAG and 1 microM IP3. The response to OAG was not inhibited by aspirin and could not be reproduced by the addition of a phorbol ester, which suggests that it involves neither arachidonic acid metabolism nor protein kinase C activation. The time course of OAG-induced 45Ca release, which was slower than IP3-induced 45Ca release, corresponded to the time course of conversion of the OAG to 1-oleoyl-2-acetoyl phosphatidic acid (OAG-PA). When either OAG-PA or lysophosphatidic acid was added to the saponin-treated platelets, the extent of 45Ca release was similar to that observed with OAG, but both the OAG-PA and the lysophosphatidic acid were 5 to 10 times more potent than OAG on a molar basis. These data suggest: that the Ca release caused by diacylglycerol is actually due to formation of phosphatidic acid and/or lysophosphatidic acid, that these molecules are not acting as simple Ca ionophores and that diacylglycerol metabolites may augment the changes in Ca homeostasis caused by IP3 during platelet activation.
D000255:Adenosine Triphosphate / Q000378:metabolism; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000502:physiology*; D002118:Calcium / Q000097:blood*; D004075:Diglycerides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005989:Glycerides / Q000494:pharmacology*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000494:pharmacology*; D007425:Intracellular Membranes / Q000378:metabolism; D008246:Lysophospholipids; D010712:Phosphatidic Acids / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D012503:Saponins; D012701:Serotonin / Q000378:metabolism; D013403:Sugar Phosphates / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004075:Diglycerides; D005989:Glycerides; D007295:Inositol Phosphates; D008246:Lysophospholipids; D010712:Phosphatidic Acids; D012503:Saponins; D013403:Sugar Phosphates; D012701:Serotonin; D015544:Inositol 1,4,5-Trisphosphate; D000255:Adenosine Triphosphate; D013755:Tetradecanoylphorbol Acetate; D001241:Aspirin; D002118:Calcium; D007213:Indomethacin