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.
D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D004357:Drug Synergism; D006863:Hydrogen-Ion Concentration; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008958:Models, Molecular; D008968:Molecular Conformation; D010743:Phospholipids / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D013453:Sulfonylurea Compounds / Q000494:pharmacology*
D007004:Hypoglycemic Agents; D010743:Phospholipids; D013453:Sulfonylurea Compounds; D012964:Sodium; D011188:Potassium; D002118:Calcium