The receptor for antidiabetic sulfonylureas controls the activity of the ATP-modulated K+ channel in insulin-secreting cells.
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.
D007516:Adenoma, Islet Cell / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D002460:Cell Line; D005905:Glyburide / Q000378:metabolism / Q000502:physiology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007340:Insulinoma / Q000378:metabolism*; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D012413:Rubidium / Q000378:metabolism
D007004:Hypoglycemic Agents; D007473:Ion Channels; D000255:Adenosine Triphosphate; D012413:Rubidium; D011188:Potassium; D005905:Glyburide