TRANSMEMBRANE SODIUM AND POTASSIUM GRADIENTS MODULATE HISTAMINE-SECRETION INDUCED BY IONOPHORE A23187

Histamine secretion was induced from rat peritoneal mast cells by Ca ionophore A23187 in the presence of various extracellular Ca concentrations. Transmembrane Na and K gradients were altered by cold pretreatment of mast cells or through the inhibition of Na-K ATPase by the use of ouabain or K-deprivation. Such pretreatments led to a parallel shift to the left of the extracellular Ca concentration-histamine secretion curve, i.e., to an apparent decrease of extracellular Ca requirement for the ionophore-induced histamine release. These effects were fully reversed by warming mast cells, by washing out ouabain or by adding K. Metabolic inhibition of mast cells prevented the ionophore-induced secretion in all the experimental conditions described. Secretion observed in the absence of added Ca was inhibited by short term treatment of cells with 5 .times. 10-6 M EGTA [ethylene glycol bis (.beta.-amino-ethyl ether) N,N,N'',N'',-tetraacetic acid] or EDTA provided Mg was absent from the assay medium. Ionophore A23187 was able to induce secretion in the presence of micromolar concentrations of extracellular Ca, when the efficiency of the ionophore was not decreased by extracellular Mg and when transmembrane Na and K gradients were altered.