An endogenous inhibitor of PAF-induced platelet aggregation, isolated from rat liver, has been identified as free fatty acid.

In an earlier study (Miwa, M., Hill, C., Kumar, R., Sugatani, J., Olson, M.S. and Hanahan, D.J. (1987) J. Biol. Chem. 262, 527-530) an inhibitor of PAF-induced aggregation of platelets was isolated from perfused rat liver. However, its structure was not established at that time. In this current investigation, the nature of this particular inhibitor was determined and found to be a mixture of long-chain unsaturated fatty acids. These acids ranged in chain length from 17 to 22. Individual chain length acids had IC50 values from 4.5 to 140 microM. Saturated fatty acids had no inhibitory properties even at concentrations well above their critical micellar concentrations. Hence, perturbation of membrane structure appears not to be the primary mode of action of these long-chain unsaturated fatty acids. These findings could have interesting connotations as regards modulation of PAF activity.