• Alexandru Babes, Michael J M Fischer, Milos Filipovic, Matthias A Engel, Maria-Luiza Flonta, and Peter W Reeh.
• Institute of Physiology and Pathophysiology, Friedrich-Alexander University Erlangen-Nuremberg, Universitaetsstrasse 17, 91054 Erlangen, Germany. alex@biologie.kappa.ro
• Eur. J. Pharmacol. 2013 Mar 15; 704 (1-3): 15-22.

AbstractThe anti-diabetic drug glibenclamide inhibits K(ATP) channels in pancreatic β-cells and stimulates insulin release. It also causes adverse effects, among which are abdominal pain, gastrointestinal disturbances and nocturia. We report that glibenclamide activates human TRPA1 in a concentration range that is commonly used to induce inhibition of K(ATP) channels in vitro. Glibenclamide generates calcium transients in HEK293t cells transiently transfected with human TRPA1, which are inhibited by the selective TRPA1 antagonist HC030031 and also evokes outwardly rectifying currents mediated by recombinant TRPA1. Glibenclamide activates a subpopulation of mouse primary sensory neurons, most of which are also sensitive to the selective TRPA1 agonist mustard oil. This glibenclamide sensitivity is completely abolished by genetic ablation of TRPA1. Taken together, our data demonstrate that glibenclamide is an agonist of human TRPA1, which may explain some of the adverse effects of the drug.Copyright © 2013 Elsevier B.V. All rights reserved.

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