Characterization and significance of sulfonylurea receptors.
This study describes and characterizes a putative sulfonylurea receptor. The radioligand used was [3H]glipizide (9 Ci/mmol). The beta-cell plasma membranes were derived from a transplantable rat insulinoma generated by subcutaneous injection of RINm5F cells and purified by ultracentrifugation on a 15-55% sucrose gradient. Specific binding of [3H]glipizide to purified beta-cell plasma membranes was determined to be maximal at temperatures of 4-23 degrees C, pH 7.3, and an incubation of 2 h. Scatchard analysis indicated a single binding site with Kd = 7 nM and sulfonylurea binding of 0.93 pmol/mg membrane protein. Displacement of [3H]glipizide from the purified beta-cell plasma membranes by various sulfonylureas and their analogues correlated well with their known hypoglycemic and insulin-releasing activities. Various agents, including nutrients, agents affecting Ca2+ flux, gastrointestinal hormones, and pancreatic hormones, had no effect on [3H]glipizide binding to the beta-cell plasma membranes. Putative sulfonylurea receptors on beta-cell and brain cell plasma membranes have been reported by several groups of investigators. Sulfonylurea binding to the beta-cell is hypothesized to close an ATP-sensitive K+ channel, which leads to depolarization of the membrane and activation of a voltage-dependent Ca2+ channel.
Department of Medicine, State University of New York, Brooklyn 11203.
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Siconolfi-Baez
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Banerji
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Lebovitz
D018528:ATP-Binding Cassette Transporters; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism / Q000502:physiology / Q000648:ultrastructure; D007340:Insulinoma / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure*; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D051381:Rats; D011955:Receptors, Drug / Q000032:analysis* / Q000378:metabolism / Q000502:physiology; D013453:Sulfonylurea Compounds / Q000378:metabolism; D064233:Sulfonylurea Receptors; D014407:Tumor Cells, Cultured
D018528:ATP-Binding Cassette Transporters; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D013453:Sulfonylurea Compounds; D064233:Sulfonylurea Receptors