Valinomycin, a degranulating agent in rat mast cells which inhibits calcium-uptake

The effect of valinomycin on both, mast cell histamine release and on calcium (45Ca)-uptake processes was examined. Pleural and peritoneal mast cells were purified in isotonic Percoll (pH = 7) and mixed populations were used in the experiments. Valinomycin (10(-9)-10(-5) M) stimulated histamine release in isolated rat mast cells when the incubation medium contained high K+ concentrations (Tris-K+ with 150 mM K+), but not in other media such as Tris-Na+ (120 mM Na+) or Tris-sucrose (300 mM sucrose). In contrast, in the absence of valinomycin, elevated K+ levels in the external environment did not activate mast cell secretion. Optimum response in valinomycin-treated mast cells was obtained when the cells were incubated for 60 min. Also valinomycin (10(-5) M) induced substantial inhibition of 45Ca-uptake while lower doses (10(-9)-10(-7) M) did not affect or only slightly increased uptake. In this paper valinomycin is shown to be a degranulating agent eliciting mediator release in mast cells incubated in the presence of high K+ levels, which does not require extracellular calcium and inhibits 45Ca uptake. The possibility that valinomycin acts as a K+ ionophore, as in other secretory systems, is discussed.