1-arachidonyl-monoglyceride causes platelet aggregation: indirect evidence for an acylglycerol acylhydrolase involvement in the release of arachidonic acid for prostaglandin synthesis.
Phosphatidylcholine liposomes containing 1-arachidonyl-monoglyceride were found to cause aggregation of human platelets. In contrast, addition of phosphatidylcholine liposomes, 1-arachidonyl-monoglyceride, or phosphatidylcholine liposomes containing I-oleoyl-monoglyceride to a similar platelet preparation had no effect. Aggregation stimulated by 1-arachidonyl-monoglyceride was inhibited by 100 microM aspirin or 1 microM indomethacin, suggesting that the arachidonic acid is first released by; a platelet acylglycerol acylhydrolase and then converted to PGG2 and thromboxane A2 which initiate the platelet aggregation. Changes in platelet morphology in response to 1-arachidonyl-monoglyceride were similar to those reported previously to occur following stimulation of platelets by arachidonic acid or PGG2 providing further support for this concept. EDTA inhibited aggregation of platelets but no shape change or granule centralization in response to 1-arach-idonyl-monoglyceride. PGE1 and theophylline inhibited both aggregation and morphological changes. These results with inhibitors are similar to the effects of these inhibitors on PGG2 and provide further evidence for similarity between the action of 1-arachidonyl-monoglyceride and PGG2. The results provide important evidence to support the concept that an acylglycerol acylhydrolase may be involved in arachidonic acid release and platelet aggregation.
D001095:Arachidonic Acids / Q000378:metabolism*; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000201:enzymology* / Q000648:ultrastructure; D005989:Glycerides / Q000494:pharmacology*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008081:Liposomes / Q000378:metabolism; D008245:Lysophospholipase / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000494:pharmacology; D010740:Phospholipases / Q000378:metabolism*; D010974:Platelet Aggregation / Q000187:drug effects*; D011453:Prostaglandins / Q000096:biosynthesis*
D001095:Arachidonic Acids; D005989:Glycerides; D008081:Liposomes; D010713:Phosphatidylcholines; D011453:Prostaglandins; C005953:monoolein; D010740:Phospholipases; D008245:Lysophospholipase; C026433:1-arachidonyl monoglyceride; D001241:Aspirin; D007213:Indomethacin