ArticleFrontiers in pharmacology2013
The pungent substances piperine, capsaicin, 6-gingerol and polygodial inhibit the human two-pore domain potassium channels TASK-1, TASK-3 and TRESK.
Article in Frontiers in pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 32 citations in OpenAlex.
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- Subunit-specific inhibition of BK channels by piperine.Biophysical journal · 2024Article
- Drimane Sesquiterpene Aldehydes ControlInternational journal of molecular sciences · 2022Article
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- Effect of 158 herbal remedies on human TRPV1 and the two-pore domain potassium channels KCNK2, 3 and 9.Journal of traditional and complementary medicine · 2020Article
- Chemogenic Subqualities of Mouthfeel.Chemical senses · 2019Review
- Natural Negative Allosteric Modulators of 5-HT₃ Receptors.Molecules (Basel, Switzerland) · 2018Review
- Selective and state-dependent activation of TRESK (KBritish journal of pharmacology · 2017Article
- Clinical concentrations of chemically diverse general anesthetics minimally affect lipid bilayer properties.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- The Effect of Pungent and Tingling Compounds fromFrontiers in pharmacology · 2017Article
- Antinociceptive activity of transient receptor potential channel TRPV1, TRPA1, and TRPM8 antagonists in neurogenic and neuropathic pain models in mice.Journal of Zhejiang University. Science. B · 2015Article
- RNA-Seq Analysis of Human Trigeminal and Dorsal Root Ganglia with a Focus on Chemoreceptors.PloS one · 2015Article
- Potent and selective inhibitors of the TASK-1 potassium channel through chemical optimization of a bis-amide scaffold.Bioorganic & medicinal chemistry letters · 2014Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
For a long time, the focus of trigeminal chemoperception has rested almost exclusively on TRP channels. However, two-pore domain (K2P) potassium channels have recently been identified as targets for substances associated with typical trigeminal sensations, such as numbing and tingling. In addition, they have been shown to be modulated by several TRP agonists. We investigated whether the pungent substances piperine, capsaicin, 6-gingerol and polygodial have an effect on human K2P channels. For this purpose, we evaluated the effects of these pungent substances on both wild-type and mutant K2P channels by means of two-electrode voltage-clamp experiments using Xenopus laevis oocytes. All four pungent substances were found to inhibit the basal activity of TASK-1 (K2P 3.1), TASK-3 (K2P 9.1), and TRESK (K2P 18.1) channels. This inhibitory effect was dose-dependent and, with the exception of polygodial on TASK-1, fully reversible. However, only piperine exhibited an IC50 similar to its reported EC50 on TRP channels. Finally, we observed for TASK-3 that mutating H98 to E markedly decreased the inhibition induced by piperine, capsaicin, and 6-gingerol, but not by polygodial. Our data contribute to the relatively sparse knowledge concerning the pharmacology of K2P channels and also raise the question of whether K2P channels could be involved in the pungency perception of piperine.
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