INHIBITION OF PLATELET TYPE-II PHOSPHOLIPASE A(2) BY AN ACYLAMINO PHOSPHOLIPID DOES NOT ALTER ARACHIDONATE LIBERATION

An acylamino phospholipid analogue (2-(R)-N-palmitoylnorleucinol-1-pho sphoglycol or (R)-PNPG) was examined for its inhibitory effects agains t type II phospholipase A(2) (PLA(2)) acting on membranes from Escheri chia coli. Using two enzyme sources (rat platelet membranes os recombi nant human type II PLA(2)), (R)-PNPG inhibited phospholipid hydrolysis to a maximal value of 80-85%, half-maximal effect being attained at a substrate/inhibitor molar ratio of 80-250. In contrast, (S)-PNPG was 12-fold less potent and thus provided a control for possible non-speci fic effects of these polar lipids. However, both analogues exerted onl y marginal effects on the liberation of [H-3]arachidonic acid from rat platelets challenged with calcium ionophore A23187. Since, among vari ous animal species, rat platelets contain by far the highest amounts o f this enzyme, our data rule out any possible involvement of secretory PLA(2) in arachidonic acid liberation from platelet phospholipids, cy tosolic PLA(2) appearing in this case as the best candidate able to re gulate eicosanoid biosynthesis.