PAF-agonistic and -antagonistic behaviour of new synthetic ether phospholipids. I. Studies on blood platelets in vitro.

Structural analogues of platelet-activating factor (PAF, 1-O-alkyl-2-O-acetyl-sn-glycero-3-phosphocholine) in which the acetyl group and the polar head have been replaced by ethyl and a pyridine ring, respectively, were tested for biological activities on blood platelets in vitro. In comparison with PAF most of the analogues exerted weak pro-aggregatory effects and both structural modifications were found to contribute to the lowering of platelet-stimulating activity. 1-O-Hexadecyl-2-O-ethyl-rac-glycero-3-phosphoric acid 4-(N,N-dimethylamino)-pyridinium ethylester (DMAP-ethyl-PAF) did not activate platelets but inhibited PAF-induced platelet responses. The inhibition was concentration-dependent and of competitive type. KB values for inhibiting the PAF-induced aggregation of human and rabbit platelets in plasma were 3.2 and 0.55 mumol/l, respectively. There is also evidence that the PAF-antagonistic behaviour of DMAP-ethyl-PAF is attributable to an inhibition of the binding of PAF to its putative receptor.