title: Sulfonylurea receptors and ATP-sensitive K+ channels in clonal pancreatic alpha cells. Evidence for two high affinity sulfonylurea receptors.
abstract: We tested for the presence of sulfonylurea receptors in pancreatic alpha cells. Two high affinity sulfonylurea receptors were identified in clonal pancreatic alpha cells (alpha TC-6): a 140-kDa species observed previously in clonal pancreatic beta cells (HIT) and a second 150-kDa protein. The dissociation constant (Kd) for both receptors is approximately 3.5 nM for an iodinated glyburide analog, 5-iodo-2-hydroxyglyburide. The estimated number of receptors (Bmax) increases approximately 2-fold, from 3.1 to 6.8 pmol/mg of membrane protein as the pH of the binding buffer is reduced from 7.5 to 6. Consistent with the notion that high affinity sulfonylurea receptors are integral components of the ATP-sensitive K+ channel, we demonstrated the presence of ATP-sensitive K+ channels in inside-out patches of alpha TC-6 cells. Whole cell K+ currents that activated with time showed inward rectification at positive potentials (above 0 mV) and were almost completely suppressed by 5 nM glyburide. Likewise, glyburide blocked 86Rb+ efflux from ATP-depleted alpha TC-6 cells, an effect that was reversed by 400 microM diazoxide. The presence of sulfonylurea receptors provides a mechanism by which sulfonylureas can directly modulate alpha cell function. The properties of the 150-kDa receptor and the role of ATP-sensitive K+ channels in alpha cells remain to be elucidated, but as in beta cells, ATP-sensitive K+ channels may be involved in metabolic regulation of alpha cells by glucose.
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, Texas 77030.
authors.forename: A S
authors.initials: AS
authors.lastname: Rajan
authors.forename: L
authors.initials: L
authors.lastname: Aguilar-Bryan
authors.forename: D A
authors.initials: DA
authors.lastname: Nelson
authors.forename: C G
authors.initials: CG
authors.lastname: Nichols
authors.forename: S W
authors.initials: SW
authors.lastname: Wechsler
authors.forename: J
authors.initials: J
authors.lastname: Lechago
authors.forename: J
authors.initials: J
authors.lastname: Bryan
mesh_terms: D018528:ATP-Binding Cassette Transporters; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D001692:Biological Transport; D002999:Clone Cells; D005934:Glucagon / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism* / Q000502:physiology; D008564:Membrane Potentials; D051379:Mice; D008822:Mice, Transgenic; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug / Q000378:metabolism*; D012413:Rubidium / Q000378:metabolism; D064233:Sulfonylurea Receptors
chemical_list: D018528:ATP-Binding Cassette Transporters; D007328:Insulin; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D000255:Adenosine Triphosphate; D005934:Glucagon; D012413:Rubidium