Sulfonylurea receptors and mechanism of sulfonylurea action.
Binding of hypoglycemic sulfonylureas and their analogues to the sulfonylurea receptor in the beta-cell plasma membrane mediates closure of the ATP-sensitive K+-channel (KATP-channel) and thereby stimulation of insulin release. The sulfonylurea receptor is a member of the traffic ATPase family with two intracellular nucleotide binding folds. The receptor binding site for hypoglycemic drugs is located at the cytoplasmic face of the plasma membrane. Mutations in the sulfonylurea receptor gene have been detected which cause familial hyper-insulinism. Non-beta-cell sulfonylurea receptors do not contribute to the therapeutic benefit of sulfonylureas, but might be involved in presumed adverse effects of sulfonylureas in the cardiovascular and the central nervous system.
Panten
U
U
Institut für Pharmakologie und Toxikologie, Technische Universität Braunschweig, Germany.
Schwanstecher
M
M
Schwanstecher
C
C
D018528:ATP-Binding Cassette Transporters; D000251:Adenosine Triphosphatases / Q000096:biosynthesis; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D015870:Gene Expression; D006801:Humans; D007004:Hypoglycemic Agents / Q000378:metabolism / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000378:metabolism*; D009928:Organ Specificity; D015221:Potassium Channels / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D013453:Sulfonylurea Compounds / Q000378:metabolism / Q000494:pharmacology*; D064233:Sulfonylurea Receptors
D018528:ATP-Binding Cassette Transporters; D007004:Hypoglycemic Agents; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D013453:Sulfonylurea Compounds; D064233:Sulfonylurea Receptors; D000251:Adenosine Triphosphatases