The anti-diabetic drug glibenclamide is an agonist of the transient receptor potential Ankyrin 1 (TRPA1) ion channel

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...

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Bibliographic Details
Published in:European journal of pharmacology 2013-03, Vol.704 (1-3), p.15-22
Main Authors: Babes, Alexandru, Fischer, Michael J.M., Filipovic, Milos, Engel, Matthias A., Flonta, Maria-Luiza, Reeh, Peter W.
Format: Article
Language:English
Subjects:
Acetanilides - pharmacology
adenosine triphosphate
adverse effects
agonists
Animals
antagonists
calcium
Calcium - physiology
Calcium Channels - physiology
Cells, Cultured
Cysteine - physiology
Diabetes
Diazoxide - pharmacology
Dorsal root ganglion
drugs
Ganglia, Spinal - cytology
gastrointestinal system
glibenclamide
Glyburide - pharmacology
HEK293 Cells
Humans
Hypoglycemic Agents - pharmacology
insulin
ion channels
islets of Langerhans
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
mustard oil
Nerve Tissue Proteins - agonists
Nerve Tissue Proteins - physiology
Pain
Purines - pharmacology
Recombinant Proteins - agonists
sensory neurons
Sensory Receptor Cells - drug effects
Sensory Receptor Cells - physiology
Sulphonylurea
Transient Receptor Potential Channels - agonists
Transient Receptor Potential Channels - physiology
TRP channel
TRPA1 Cation Channel
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Summary: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.
ISSN:0014-2999
1879-0712
DOI:10.1016/j.ejphar.2013.02.018