Platelet-activating factor. Evidence for 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine as the active component (a new class of lipid chemical mediators)

Abstract

A glyceryl ether containing phosphoglyceride, 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine (Ac-GEPC), has been shown to have a biological activity indistinguishable from that of naturally generated (rabbit) platelet activating factor (PAF). Its biochemical and biological properties so closely parallel those of naturally occurring PAF that we propose they are one and the same compound. Both PAF and AcGEPC could be converted to an inactive form through base-catalyzed methanolysis and restored to 100% functional activity by reaction with acetic anhydride. The synthetic lipid, AcGEPC, elicited 50% secretion of serotonin from rabbit platelets at a level of 10(-10) M (based on phosphorus). A propionyl derivative had somewhat comparable activity towards platelets, whereas the butyryl homologue was some 7-fold less active and the stearoyl derivative was inactive. These short chain acylglyceryl ether phosphoglycerides represent an entirely new, potent and unique class of lipid chemical mediators. 1-Acyl-2-acetyl-sn-glyceryl-3-phosphorylcholine (AcLL) also exhibited activity towards platelets but was some 200-fold less active than AcGepc. the propionyl lysolecithin behaved quite similarly to AcLL, but butyryl and stearoyl lysolecithins showed no activity.