Inhibition by calcium antagonists of histamine release and calcium influx of rat mast cells: difference between induction of histamine release by concanavalin A and compound 48/80.

The relation between calcium influx and histamine release from rat mast cells was investigated. When purified mast cells pretreated with a calcium antagonist (MnCl2 or methoxyverapamil (D-600)) were exposed to concanavalin A or compound 48/80 in Tyrode solution (pH 7.4) at 37 degrees C, the calcium antagonists inhibited the extracellular calcium-dependent component of concanavalin A-induced histamine release. MnCl2 also inhibited the extracellular calcium-dependent component of compound 48/80-induced histamine release, whereas D-600 did not inhibit the release. D-600 inhibited the 45Ca uptake induced by concanavalin A, but did not inhibit the 45Ca uptake induced by compound 48/80. It was found that the inhibitory action of calcium antagonists depended on the uptake of extracellular calcium. These observations suggest that concanavalin A and compound 48/80 stimulate different mechanisms of calcium influx. Studies on inactivation of the mechanisms of calcium influx showed that calcium influx into cells activated by concanavalin A stopped when concanavalin A was washed out, whereas the influx activated by compound 48/80 was still operative after compound 48/80 had been washed out.