Species difference in the specific receptors of platelet activating factor

Abstract

Relative potencies of platelet activating factor (PAF) and PAF analogs and several PAF receptor antagonists when inhibiting the [ 3H]PAF specific binding to human and rabbit platelet membranes and membrane fragments of human lung tissues were compared. In rabbit platelets, L-652,731 was found to be most potent in the list of PAF receptor antagonists with an equilibrium inhibition constant ( K i ) of 9.83 (±2.92) × 10 −9 M followed by L-653,150 > kadsurenone ⋍ Ono-6240 > ginkgolide B > CV-3988 > L-651,142 , whereas in human platelets the relative potencies of these PAF receptor antagonists were as follows: Ono-6240 > L-653,150 ⋍ L-652,731 ⋍ kadsurenone > ginkgolide B > CV-3988 > L-651,142 . Ono-6240 was the most potent one with a K i of 4.86 (±1.44) × 10 −8 M which was roughly two times more potent than that in rabbit platelets, whereas the affinity of L-652,731 was about ten times less in human platelets ( K i = 1.03 (±0.15) × 10 −7 M) compared to that in rabbit platelets ( K i = 9.83 (±2.92) × 10 −9 M). These variations between species among PAF antagonists strongly suggest that there exists a species difference at or near the binding site of the receptor of platelet activating factor. The relative potency of these PAF receptor antagonists in human lung membranes differed very little from that in human platelets and was found to be Ono-6240 > L-653,150 ⋍ kadsurenone ⋍ L-652,731 > ginkgolide B > CV-3988 > L-651,142 . Even though C 16-PAF showed slightly higher potency in human lung, and CV-3988 and Ono-6240 showed slightly lower, the difference was too small to suggest that there is a difference in the PAF receptors between human platelets and human lung tissues.