Sulfonylurea receptors and ATP-sensitive K+ channels in clonal pancreatic α cells: Evidence for two high affinity sulfonylurea receptors

A. S. Rajan, L. Aguilar-Bryan, D. A. Nelson, C. G. Nichols, S. W. Wechsler, J. Lechago, J. Bryan

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37 Scopus citations

Abstract

We tested for the presence of sulfonylurea receptors in pancreatic a cells. Two high affinity sulfonylurea receptors were identified in clonal pancreatic a cells (αTC-6): a 140-kDa species observed previously in clonal pancreatic β cells (HIT) and a second 150-kDa protein. The dissociation constant (Kd) for both receptors is ∼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 αTC-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 αTC-6 cells, an effect that was reversed by 400 μM diazoxide. The presence of sulfonylurea receptors provides a mechanism by which sulfonylureas can directly modulate a cell function. The properties of the 150-kDa receptor and the role of ATP-sensitive K+ channels in a cells remain to be elucidated, but as in β cells, ATP-sensitive K+ channels may be involved in metabolic regulation of a cells by glucose.

Original languageEnglish
Pages (from-to)15221-15228
Number of pages8
JournalJournal of Biological Chemistry
Volume268
Issue number20
StatePublished - Jul 15 1993

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