Effect of hypoglycemic sulfonylureas on Ca2+ fluxes across lipid bilayers.
Black lipid membranes and liposomes loaded with Ca2+ or 5,6-carboxyfluorescein were used for exploring the mechanism of action of insulin-releasing sulfonylureas. Unlike the Ca2+/H+ exchanging ionophore A-23187, tolbutamide did not stimulate the net efflux of Ca2+ from the liposomes. Glibenclamide caused a sustained release of Ca2+, but this effect could be attributed to labilization of the liposomal membrane as indicated by a quantitatively similar loss of the stability marker 5,6-carboxyfluorescein. Unlike the neutral ionophore nonactin or the channel forming quasi-ionophore gramicidin A, the sulfonylureas did not alter the conductance of black lipid membranes in medium containing Na+, K+, Ca2+, Mg2+, and Cl-. It is concluded that the sulfonylureas tested lack ionophore properties but that glibenclamide can labilize membranes.
D001692:Biological Transport / Q000187:drug effects; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D006096:Gramicidin / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007473:Ion Channels / Q000378:metabolism; D007476:Ionophores; D008051:Lipid Bilayers; D008081:Liposomes / Q000378:metabolism*; D008563:Membrane Lipids / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013453:Sulfonylurea Compounds / Q000494:pharmacology*
D007004:Hypoglycemic Agents; D007473:Ion Channels; D007476:Ionophores; D008051:Lipid Bilayers; D008081:Liposomes; D008563:Membrane Lipids; D013453:Sulfonylurea Compounds; D006096:Gramicidin; D000001:Calcimycin; D002118:Calcium