Natural 1-O-alkylglycerols reduce platelet-activating factor-induced release of [3H]-serotonin in rabbit platelets.
Natural 1-O-alkylglycerols have multiple biological activities with distinct mechanisms. In THP-1 monocytes, they amplify platelet-activating factor production. In endothelial cells, they participate in the production of 1-O-alkyl-2-acyl-sn-glycerol, a PKC inhibitor. Since PAF as well as PKC may interfere with platelet functions, we studied the effect of natural alkylglycerols purified from shark liver oil on [3H]-serotonin release from rabbit platelets in vitro. [3H]-alkylglycerols (1 microM) were consistently incorporated into platelet lipids and after a 2-h incubation, they were metabolised into phosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol, which represented 53.5+/-1.7%, 36.3+/-1.8%, 5.3+/-0.5% of metabolised [3H]-alkylglycerols, respectively. Alkylglycerols (10 microM) had no effect on spontaneous [3H]-serotonin release. However, alkylglycerols partially inhibited PAF-induced [3H]-serotonin release while they did not modify thrombin-induced release. These data show that alkylglycerols inhibit partially and specifically PAF-induced platelet stimulation and suggest that this effect could result from interfering with PAF receptors.
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Laboratoire de Pharmacologie Moléculaire, Faculté des Sciences Pharmaceutiques et Biologiques, Université de Rennes I, 2 avenue du Pr Léon Bernard, 35043 Rennes Cedex, France.
Cheminade
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Legrand
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D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D005995:Glyceryl Ethers / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000494:pharmacology*; D015539:Platelet Activation / Q000187:drug effects*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011817:Rabbits; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D013917:Thrombin / Q000378:metabolism
D005995:Glyceryl Ethers; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D012701:Serotonin; D011493:Protein Kinase C; D013917:Thrombin