Stoichiometry of calcium binding by hypoglycemic sulfonylureas.

In a two-phase bulk system for the study of Ca ionophoresis, certain hypoglycemic sulfonylureas, when added to the organic phase, were translocated into the aqueous medium. Nevertheless, the stoichiometry of Ca binding by these agents could be assessed by repeated mixing of the aqueous medium with organic phases. At saturation, the binding of Ca ranged from 0.5 to 1.0 mole/mole of sulfonylurea. A 1:1 molar ratio was observed with glibenclamide, and this was found to be compatible with the conformational analysis of the Ca-glibenclamide complex. There was a tight correlation between the stoichiometry of the Ca-sulfonylurea complex and the biological potency of each drug. This suggests that such a stoichiometry may be responsible, in part at least, for differences in the insulinotropic capacity of distinct hypoglycemic sulfonylureas.