Calcium dependency of inhibition by arachidonic acid of compound 48/80-induced histamine release from mast cells

Abstract

Compound 48/80 (compd 48/80)-induced histamine secretion from rat mast cells was inhibited almost completely by pretreatment of the cells at 37° with 25 μM arachidonic acid in the presence of 1.8 mM Ca 2+. As the Ca 2+ concentration was reduced below 1.8 mM, 25 μM arachidonic acid became less inhibitory and, then, progressively more stimulatory for histamine release with or without compd 48/80. No additive effect on histamine release was obtained by combining compd 48/80 and arachidonic acid. Pretreatment of mast cells with lidocaine, an inhibitor of Ca 2+ binding to phospholipid, or with nordihydroguaiaretic acid, an inhibitor of Ca 2+ flux and lipoxygenase, stimulated arachidonic acid-induced histamine release. Arachidonic acid also inhibited a compd 48/80-induced spike increment of intracellular 45Ca 2+ uptake and a decrease of total 45Ca 2+ uptake by 45Ca 2+-preloaded mast cells. Arachidonic acid and Ca 2+ also suppressed melittin-induced histamine release and compd 48/80-induced release of radioactivity from mast cells preloaded with [ 3H]arachidonic acid. These results suggest that exogenous arachidonic acid or its metabolite(s) may interact with membrane-associated Ca 2+, disturbing Ca 2+ availability for the trigger mechanism of compd 48/80-induced histamine release or inhibiting the subsequent metabolism of arachidonic acid via the lipoxygenase pathway to form active metabolites involved in the histamine liberating mechanism.