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.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes; D003594:Cytoplasmic Granules / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006636:Histamine Release / Q000187:drug effects; D007700:Kinetics; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014634:Valinomycin / Q000494:pharmacology*
D002132:Calcium Radioisotopes; D014634:Valinomycin; D011188:Potassium; D002118:Calcium