Specific desensitization of rabbit platelets by platelet-activating factor (PAF-acether) and derivatives.

PAF-acether is a 1-O-alkyl-2 acetyl-sn-glycerol-3-phosphorylcholine which triggers platelet aggregation independently from ADP release and thromboxane A2 formation. PAF-acether-aggregated rabbit platelets did not respond to a second challenge with the same agonist, but still aggregated to arachidonic acid. This desensitization to PAF-acether was a dose-dependent phenomenon. Specific cross-desensitization to PAF-acether was achieved using PAF-acether from four cellular origins, synthetic PAF-acether and its 2-propionyl analogue. Conversely, 2-lyso-PAF-acether and PAF-acether enantiomer were unable to induce specific desensitization. These results suggest that PAF-acether, whatever its origin, exhibits identical active molecular site, and that the presence and the stereospecific position of the 2-acetyl group are critical for the interaction of PAF-acether with platelets.