Synergistic effect of hypoglycemic sulfonylureas and negative phospholipids on calcium transport: ionic and conformational aspects.

In a two-phase bulk system for the study of ionophoresis, the capacity of hypoglycemic sulfonylureas to translocate Ca2+ was enhanced in a synergistic manner by negatively charged phospholipids. High concentrations of Na+ or K+ had relatively little effect on sulfonylurea-mediated Ca2+ translocation. The acidity constant of hypoglycemic sulfonylureas ranged from 10(-5) to 10(-6). The conformation analysis of Ca2+ -gliquidone complexes with a 1:1 or 1:2 stoichiometry and of a hybrid complex between Ca2+ and both gliquidone and phosphatidylserine revealed configurations suitable for Ca2+ transport across a hydrophobic domain. These findings raise the possibility that the cationic response of the pancreatic B-cell to hypoglycemic sulfonylureas may be due primarily to an alteration of both Ca2+ and H+ transport.