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J. Biol. Chem., Vol. 262, Issue 33, 15840-15844, 11, 1987
H Schmid-Antomarchi, J De Weille, M Fosset and M Lazdunski
Sulfonylureas are powerful hypoglycemic drugs that have been used for
decades to treat diabetic patients. This paper describes a 86Rb+ flux
technique that permits one to study easily the properties of ATP- modulated
K+ channels in RINm5F insulinoma cells. Sulfonylureas inhibit this type of
K+ channel under conditions of intracellular ATP depletion. The most potent
sulfonylureas (glibenclamide, glipizide, and gliquidone) are acting in the
nanomolar range of concentration. Inhibition of the single ATP-modulated K+
channels by low concentrations of sulfonylureas was also observed using the
patch-clamp technique. The sulfonylurea receptor has been biochemically
identified with [3H]glibenclamide. For 10 different sulfonylureas (or
sulfonylurea analogs) there was an excellent correlation between efficacy
of blockade of ATP-modulated K+ channels and efficacy of binding to the
sulfonylurea receptors using the 3H-ligand.
The receptor for antidiabetic sulfonylureas controls the activity of the ATP-modulated K+ channel in insulin-secreting cells [published erratum appears in J Biol Chem 1989 Jun 25;264(18):10926]
Centre de Biochimie du Centre National de la Recherche Scientifique, Nice, France.
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