Serine esterase inhibitors block stimulus-induced mobilization of arachidonic acid and phosphatidylinositide-specific phospholipase C activity in platelets.

Serine esterase inhibitors (phenylmethanesulfonyl fluoride, 5-dimethylaminonaphthalene-1-sulfonyl (dansyl) fluoride, 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate, or p-nitrophenyl anthranilate) blocked the production of malonyldialdehyde by platelets induced with a variety of stimuli (including thrombin, trypsin, collagen, and A23187). These inhibitors did not block malonyldialdehyde production by platelets from exogenous arachidonic acid. Those inhibitors studied in greater detail (phenylmethanesulfonyl fluoride and 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate) were shown to inhibit the release of [1-14C]arachidonic acid from phosphatidylinositol and phosphatidylcholine in intact platelets but not the conversion of arachidonic acid to thromboxanes, prostaglandins, or hydroxyfatty acids. These inhibitors also blocked the stimulus-induced production of [32P]phosphatidic acid in intact platelets. Both arachidonic acid release from phosphatidylinositol and phosphatidic acid production have been reported to depend on the production of diglyceride by the action on the phosphatidylinositol-specific phospholipase C.f a phosphatidylinositol-specific phospholipase C. That enzyme in the soluble fraction from disrupted platelets was inhibited at concentrations of serine esterase inhibitors which block arachidonic acid release in intact platelets. These results indicate that serine esterase inhibitors block the stimulus-induced mobilization of arachidonic acid in platelets at least in part by their action o