Alkyl chain homologs of platelet-activating factor and their effects on the mammalian heart

Platelet-activating factor (PAF; AGEPC) is a potent negative inotropic and coronary-vasoconstricting agent. Minor structural alterations in the PAF molecule are known to greatly affect its biological activity; thus, we have investigated the effects of selected synthetic saturated and unsaturated alkyl chain PAF homologs on the isolated guinea pig heart. The rank order of potency for the negative inotropic effect was C16:0- > C18:1- > beef-heart AGEPC > C15:0- > C18:0- > C14:0-AGEPC; the rank order for the coronary-vasoconstricting effect was C16:0- ≈ C18:1- ≈ beef-heart AGEPC > C15:0- > C18:0- ≈ C14:0-AGEPC. With the exception of C16:0- and C18:1-AGEPC, the relative potencies for the cardiac and coronary effects of the alkyl chain AGEPC homologs did not correlate well with their relative potencies in stimulating rabbit platelets and human neutrophils. The differences in the rank order of potency for these AGEPC homologs suggest the presence of species and/or target cell PAF receptor heterogeneity.