Differential inhibitory effects of the arachidonic acid analog ETYA on rat mast cell exocytosis evoked by secretagogues utilizing cellular or extracellular calcium.

ETYA (5,8,11,14-eicosatetraynoic acid; 50-100 microM), which inhibits both cyclo-oxygenase and lipoxidase, inhibited histamine release evoked by secretagogues dependent on extracellular calcium (antigen, dextran, and concanavalin A) but failed to inhibit secretion elicited by secretagogues capable of mobilizing calcium from intracellular sites (48/80, polymyxin B, protamine sulfate and poly-L-lysine). Responses to these latter secretagogues were inhibited only by higher concentrations of ETYA (100-200 microM) that were cytotoxic. Secretion evoked by the calcium ionophore A23187 (0.1 microgram/ml) was inhibited at much lower concentrations of ETYA (1-10 microM) but this inhibition could not be overcome by increasing the concentration of calcium. Responses to higher concentrations of ionophore were not inhibited by ETYA except in amounts affecting cell viability. Like ETYA, each of several fatty acids, including arachidonic acid, were inhibitory towards histamine release evoked by A23187 or 48/80. The results indicate that EYTA acts at some early stage of stimulus-secretion coupling rather than on the final, common, calcium-activated steps of exocytosis. Moreover, this action may be unrelated to inhibition of lipoxidase or cyclooxygenase.