Dual effect of verapamil on rat peritoneal mast cells: inhibition or induction of histamine release.

1. Verapamil (1.0 microM) inhibits histamine release from rat peritoneal mast cells induced by both compound 48/80 (Burroughs Wellcome), an external calcium-independent stimulant, and by protamine, an external calcium-dependent stimulant. 2. The inhibition was reversed by calcium in a concentration-dependent manner and thus seems to be related to the calcium-blocking action of verapamil. The inhibitory effect of 1.0 microM verapamil on protamine-induced histamine release in the presence of 0.5 mM calcium was 64%, and 32% in the presence of 2.0 mM calcium. 3. At concentrations of 0.1-1.0 mM, verapamil induces histamine release. The verapamil-induced release was independent of calcium at lower concentrations but at 1.0 mM, more release was observed in the absence of calcium. Histamine release induced by verapamil was blocked by temperature (2-4 degrees C) and by 2,4-dinitrophenol. Glucose (5 mM) reversed the effect of 2,4-dinitrophenol.