The Selective Rat Toxicant Norbormide Blocks KATP Channels in Smooth Muscle Cells But Not in Insulin-Secreting Cells

Frontiers in Pharmacology
Simona SaponaraSergio Bova


Norbormide is a toxicant selective for rats to which it induces a widespread vasoconstriction. In a recent paper, we hypothesized a role of ATP-sensitive potassium (KATP) channels in norbormide-induced vasoconstriction. The current study was undertaken to verify this hypothesis by comparing the effects of norbormide with those of glibenclamide, a known KATP channel blocker. The whole-cell patch-clamp method was used to record KATP currents in myocytes freshly isolated from the rat and mouse caudal artery and from the rat gastric fundus, as well as in insulin-secreting pancreatic beta cells (INS-1 cells). Smooth muscle contractile function was assessed on either rat caudal artery rings or gastric fundus strips. Molecular modeling and docking simulation to KATP channel proteins were investigated in silico. Both norbormide (a racemic mixture of endo and exo isomers) and glibenclamide inhibited KATP currents in rat and mouse caudal artery myocytes, as well as in gastric fundus smooth muscle cells. In rat INS-1 cells, only glibenclamide blocked KATP channels, whereas norbormide was ineffective. The inhibitory effect of norbormide in rat caudal artery myocytes was not stereo-specific as both the endo isomers (active as vasoconstricto...Continue Reading


Aug 1, 1992·The American Journal of Physiology·Y ImamuraA Takeshita
Jan 1, 1989·Progress in Biophysics and Molecular Biology·F M Ashcroft, P Rorsman
Nov 1, 1986·Journal of Medicinal Chemistry·V A AshwoodK Willcocks
Jul 1, 1966·Journal of Medicinal Chemistry·G I PoosA P Roszkowski
Sep 1, 1994·Journal of Vascular Research·K Bian, K Hermsmeyer
Jan 1, 1993·The American Journal of Physiology·W F JacksonR Busse
Oct 1, 1996·The Journal of General Physiology·A D Bonev, M T Nelson
Feb 12, 1998·The American Journal of Physiology·H YokoshikiN Sperelakis
Nov 12, 1998·Trends in Biochemical Sciences·F JeanmouginT J Gibson
Dec 9, 1998·European Journal of Pharmacology·F FusiG P Sgaragli
Jun 12, 2003·European Journal of Pharmacology·Sergio BovaFabio Fusi
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Jan 25, 2005·The Journal of Pharmacology and Experimental Therapeutics·Fabio FusiSimona Saponara
May 17, 2005·British Journal of Pharmacology·Jolanta SkalskaAdam Szewczyk
Jun 15, 2005·Biochimica Et Biophysica Acta·Fernanda RicchelliSergio Bova
Jun 28, 2005·Journal of Molecular and Cellular Cardiology·Nian-Qing ShiJonathan C Makielski
Jun 17, 2008·Journal of Smooth Muscle Research = Nihon Heikatsukin Gakkai Kikanshi·Eun A KoWon Sun Park
Jan 6, 2010·EMBO Molecular Medicine·Kenju ShimomuraFrances M Ashcroft
Jan 21, 2010·Physiological Reviews·Hiroshi HibinoYoshihisa Kurachi
Oct 11, 2011·Journal of Cheminformatics·Noel M O'BoyleGeoffrey R Hutchison
Oct 13, 2011·Molecular Systems Biology·Fabian SieversDesmond G Higgins
Apr 30, 2013·Database : the Journal of Biological Databases and Curation·Juergen HaasTorsten Schwede
Oct 10, 2013·British Journal of Pharmacology·Andrew TinkerAlison Thomas
May 8, 2014·Diabetes & Vascular Disease Research : Official Journal of the International Society of Diabetes and Vascular Disease·Lars RydénJose Luis Zamorano
Apr 16, 2015·Nucleic Acids Research·Sebastian SalentinMichael Schroeder
Dec 15, 2015·Physiological Reviews·Monique N Foster, William A Coetzee
May 20, 2016·Journal of Cheminformatics·Mathew R KoebelSuman Sirimulla
Jun 24, 2016·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Michael KittlMartin Jakab
Oct 11, 2016·Frontiers in Pharmacology·Claudio D'AmoreSergio Bova
Jan 14, 2017·Cell·Ningning LiLei Chen
Feb 17, 2018·Biochemical Pharmacology·Zhongwei Liu, Raouf A Khalil

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