Effect of TMB-8 on histamine release from isolated rat mast cells.

TMB-8 was capable of complete inhibition of the histamine release induced by antigen, compound 48/80, and the ionophore A23187 (2 microM). The effective concentrations for 50% inhibition (IC50) were 1.2 X 10(-4) M for antigen, 1.6 X 10(-4) M for compound 48/80 both in the absence and in the presence of calcium, and 0.7 X 10(-4) M for the ionophore. The inhibitory action was not affected by increased calcium concentration in the medium from 1 to 2m M. The presence of glucose in the medium counteracted the inhibition by TMB-8 and, for low concentrations of the ionophore (0.25 microM), TMB-8 caused a pronounced enhancement of the histamine release. Our results indicate that TMB-8 primarily exerts its effects by interference with oxidative metabolism rather than by affecting the intracellular calcium availability.