Lack of Ca2 lonophoretic Activity of Hypoglycemic Sulfonylureas in Excitable Cells and Isolated Secretory Granules

fl-Cell-rich pancreatic islets, neurohypophyses, and adrenal medullae were used for exploring whether hypoglycemic sulfonylureas exhibit Ca2 ionophoretic properties. Ex-posure of these excitable organs to depolarizing concentrations of K resulted in stimu-lation both of 45Ca uptake and efflux. Although tolbutamide does not bind preferentially to pancreatic islets, this sulfonylurea was specific in stimulating the fluxes of 45Ca in these endocrine specimens. A chromaffm granule preparation was used for studies of both the net transport of Ca2 with the metallochromic indicator arsenazo III and the proton concentration gradient (pH) with the fluorescent probe 9-aminoacridine. Even at high concentrations, tolbutamide and glibenclamide did not mediate Ca2’-H exchange diffu-sion whether or not the granules were made permeable to protons by the addition of the protonophore carbonyl cyanide p-trifluoromethoxyphenylhydrazone, nor did the sulfon-ylureas affect Ca2-H exchange diffusion induced by the addition of A-23187. The data indicate that the Ca2 fluxes associated with sulfonylurea-stimulated insulin secretion do not result from the Ca2-ionophoretic properties of the drugs but rather reflect depolari-zation of the fl-cells