Synergistic effects of hypoglycaemic sulphonylureas and antibiotic ionophores upon calcium translocation.

1 Hypoglycaemic sulphonylureas, such as tolbutamide and gliclazide, provoke the translocation of calcium from an aqueous medium into or across a hydrophobic region. The combined effect of sulphonylureas and antibiotic ionophores upon such a process was investigated. 2 The magnitude of the sulphonylurea-induced translocation of calcium was more marked in the presence than in the absence of A23187. Gliclazide and tolbutamide also enhanced, although less markedly, X537A-mediated calcium translocation. The effect of the sulphonylureas was even less marked in the presence of both ionophores, which acted synergistically in causing calcium translocation. 3 A non-hypoglycaemic sulphonylurea and diazoxide failed to affect ionophore-mediated calcium translocation. Gliclazide failed to enhance X537A-mediated sodium translocation. 4 It is proposed that the primary site of action of hypoglycaemic sulphonylureas upon calcium-dependent physiological processes may correspond to a drug-induced facilitation of calcium transport across the plasma membrane, as mediated by native ionophores.