![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 55, Issue 6, 1060-1066, June 1999
Brekardin,
Institut für Pharmakologie und Toxikologie, Universität
Braunschweig, Mendelssohnstra Hypoglycemic sulfonylureas (e.g., glibenclamide, glipizide, and
tolbutamide) exert their stimulatory effect on excitatory cells by
closure of ATP-sensitive potassium (KATP) channels. These channels are heteromultimers composed with a 4:4 stoichiometry of an
inwardly rectifying K+ channel (KIR)
subunit 6.x plus a sulfonylurea receptor (SUR). SUR1/KIR6.2 reconstitutes the neuronal/pancreatic e 1, 38106 Braunschweig, Germany
-cell
channel, whereas SUR2A/KIR6.2 and SUR2B/KIR6.1
(or KIR6.2) are proposed to reconstitute the cardiac and
the vascular smooth muscle-type KATP channels,
respectively. SUR2A and SUR2B are splice variants of a single gene
differing only in their C-terminal 42 amino acids. Affinities of
sulfonylureas for rat SUR2A, rat or human SUR2B, and a SUR2 chimera
containing the C-terminal 42 amino acids of SUR1 did not differ
significantly, implying that the C terminus does not form part of the
binding pocket. Consistent with these findings, reconstituted
SUR2A/KIR6.2 and SUR2B/KIR6.2 channels revealed
similar sensitivities for glibenclamide and tolbutamide. Dissociation
constants of sulfonylureas for SUR2A and SUR2B were 10- to 400-fold
higher than for SUR1, however, amazingly the benzoic acid derivative
meglitinide did not show lower affinity for SUR2 isoforms. Potencies of
glibenclamide, glipizide, tolbutamide, and meglitinide to inhibit
activity of SUR1/KIR6.2 and SUR2B/KIR6.2 channels were 3- to 6-fold higher than binding affinities of these drugs with concentration-inhibition relations being significantly steeper (Hill coefficients 1.23-1.32) than binding curves (Hill coefficients 0.93-1.06). The data establish that the C terminus of
SURs does not affect sulfonylurea affinity and sensitivity. We conclude
that occupation of one of the four SUR sites per channel complex is
sufficient to induce KATP channel closure.
This article has been cited by other articles:
|
|
 |
|
  K. Shorter, N. P. Farjo, S. M. Picksley, and V. A. Randall Human hair follicles contain two forms of ATP-sensitive potassium channels, only one of which is sensitive to minoxidil FASEB J, June 1, 2008; 22(6): 1725 - 1736. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Malester, X. Tong, I. Ghiu, A. Kontogeorgis, D. E. Gutstein, J. Xu, K. D. Hendricks-Munoz, and W. A. Coetzee Transgenic expression of a dominant negative KATP channel subunit in the mouse endothelium: effects on coronary flow and endothelin-1 secretion FASEB J, July 1, 2007; 21(9): 2162 - 2172. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Evans, A. K. Allan, S. A. Davies, and J. A. T. Dow Sulphonylurea sensitivity and enriched expression implicate inward rectifier K+ channels in Drosophila melanogaster renal function J. Exp. Biol., October 1, 2005; 208(19): 3771 - 3783. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Heissig, K. A. Urban, K. Hastedt, B. J. Zunkler, and U. Panten Mechanism of the Insulin-Releasing Action of {alpha}-Ketoisocaproate and Related {alpha}-Keto Acid Anions Mol. Pharmacol., October 1, 2005; 68(4): 1097 - 1105. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Wang, J. Su, X. Wang, H. Piao, X. Zhang, C. Y. Adams, N. Cui, and C. Jiang Subunit Stoichiometry of the Kir1.1 Channel in Proton-dependent Gating J. Biol. Chem., April 8, 2005; 280(14): 13433 - 13441. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Davis-Taber, E. J. Molinari, R. J. Altenbach, K. L. Whiteaker, C.-C. Shieh, G. Rotert, S. A. Buckner, J. Malysz, I. Milicic, J. S. McDermott, et al. [125I]A-312110, a Novel High-Affinity 1,4-Dihydropyridine ATP-sensitive K+ Channel Opener: Characterization and Pharmacology of Binding Mol. Pharmacol., July 1, 2003; 64(1): 143 - 153. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Schwanstecher and M. Schwanstecher Nucleotide Sensitivity of Pancreatic ATP-Sensitive Potassium Channels and Type 2 Diabetes Diabetes, December 1, 2002; 51(90003): S358 - 362. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Proks, F. Reimann, N. Green, F. Gribble, and F. Ashcroft Sulfonylurea Stimulation of Insulin Secretion Diabetes, December 1, 2002; 51(90003): S368 - 376. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Lange, C. Loffler-Walz, H. C. Englert, A. Hambrock, U. Russ, and U. Quast The Stereoenantiomers of a Pinacidil Analog Open or Close Cloned ATP-sensitive K+ Channels J. Biol. Chem., October 18, 2002; 277(43): 40196 - 40205. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. K. Hansen, I. T. Christensen, J. B. Hansen, R. D. Carr, F. M. Ashcroft, and P. Wahl Differential Interactions of Nateglinide and Repaglinide on the Human {beta}-Cell Sulphonylurea Receptor 1 Diabetes, September 1, 2002; 51(9): 2789 - 2795. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Hambrock, R. Preisig-Muller, U. Russ, A. Piehl, P. J. Hanley, J. Ray, J. Daut, U. Quast, and C. Derst Four novel splice variants of sulfonylurea receptor 1 Am J Physiol Cell Physiol, August 1, 2002; 283(2): C587 - C598. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Giblin, Y. Cui, L. H. Clapp, and A. Tinker Assembly Limits the Pharmacological Complexity of ATP-sensitive Potassium Channels J. Biol. Chem., April 12, 2002; 277(16): 13717 - 13723. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Loffler-Walz, A. Hambrock, and U. Quast Interaction of KATP Channel Modulators with Sulfonylurea Receptor SUR2B: Implication for Tetramer Formation and Allosteric Coupling of Subunits Mol. Pharmacol., February 1, 2002; 61(2): 407 - 414. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Russ, U. Lange, C. Loffler-Walz, A. Hambrock, and U. Quast Interaction of the Sulfonylthiourea HMR 1833 with Sulfonylurea Receptors and Recombinant ATP-Sensitive K+ Channels: Comparison with Glibenclamide J. Pharmacol. Exp. Ther., December 1, 2001; 299(3): 1049 - 1055. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Hambrock, C. Loffler-Walz, U. Russ, U. Lange, and U. Quast Characterization of a Mutant Sulfonylurea Receptor SUR2B with High Affinity for Sulfonylureas and Openers: Differences in the Coupling to Kir6.x Subtypes Mol. Pharmacol., July 1, 2001; 60(1): 190 - 199. [Abstract] [Full Text]
|
|
|
|
 |
|
 R. M Shepherd, K. E Cosgrove, R. E O'Brien, P. D Barnes, C. Ämmälä, and M. J Dunne Hyperinsulinism of infancy: towards an understanding of unregulated insulin release Arch. Dis. Child. Fetal Neonatal Ed., March 1, 2000; 82(2): 87F - 97. [Abstract] [Full Text]
|
|
|
|
|
|
I. Gross, A. Toman, I. Uhde, C. Schwanstecher, and M. Schwanstecher ACCELERATED COMMUNICATION: Stoichiometry of Potassium Channel Opener Action Mol. Pharmacol., December 1, 1999; 56(6): 1370 - 1373. [Abstract] [Full Text]
|
|
|
|
|
|
U. Russ, A. Hambrock, F. Artunc, C. Löffler-Walz, Y. Horio, Y. Kurachi, and U. Quast Coexpression with the Inward Rectifier K+ Channel Kir6.1 Increases the Affinity of the Vascular Sulfonylurea Receptor SUR2B for Glibenclamide Mol. Pharmacol., November 1, 1999; 56(5): 955 - 961. [Abstract] [Full Text]
|
|
|
|
|
|
I. Uhde, A. Toman, I. Gross, C. Schwanstecher, and M. Schwanstecher Identification of the Potassium Channel Opener Site on Sulfonylurea Receptors J. Biol. Chem., October 1, 1999; 274(40): 28079 - 28082. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
