title: The anti-diabetic drug glibenclamide is an agonist of the transient receptor potential Ankyrin 1 (TRPA1) ion channel.
abstract: The 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.
authors: Institute of Physiology and Pathophysiology, Friedrich-Alexander University Erlangen-Nuremberg, Universitaetsstrasse 17, 91054 Erlangen, Germany. alex@biologie.kappa.ro
authors: Alexandru
authors: A
authors: Babes
authors: Michael J M
authors: MJ
authors: Fischer
authors: Milos
authors: M
authors: Filipovic
authors: Matthias A
authors: MA
authors: Engel
authors: Maria-Luiza
authors: ML
authors: Flonta
authors: Peter W
authors: PW
authors: Reeh
mesh_terms: D000083:Acetanilides / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology; D015220:Calcium Channels / Q000502:physiology; D002478:Cells, Cultured; D003545:Cysteine / Q000502:physiology; D003981:Diazoxide / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology; D005905:Glyburide / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000819:agonists* / Q000502:physiology; D011687:Purines / Q000494:pharmacology; D011994:Recombinant Proteins / Q000819:agonists; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000502:physiology; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000819:agonists* / Q000502:physiology
chemical_list: C552888:2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide; D000083:Acetanilides; D015220:Calcium Channels; D007004:Hypoglycemic Agents; D009419:Nerve Tissue Proteins; D011687:Purines; D011994:Recombinant Proteins; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050051:Transient Receptor Potential Channels; D003545:Cysteine; D003981:Diazoxide; D005905:Glyburide; D002118:Calcium