ArticleFrontiers in pharmacology2022
Differential Activation of TRPM8 by the Stereoisomers of Menthol.
Article in Frontiers in pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 8 citations in OpenAlex.
- Temperature-Dependent Menthol Binding across TRPM8 Conformational States.Journal of the American Chemical Society · 2026Article
- Molecular mechanism of menthol-induced TRPV5 channel inhibition.Nature communications · 2026Article
- The tip of the iceberg: Profiling cooling agents using computational approaches to inform tobacco regulatory science.PloS one · 2026Article
- A novel TRPV5/6-like channel from a scleractinian coral.PloS one · 2025Article
- Irritant-evoked reflex tachyarrhythmia in spontaneously hypertensive rats is reduced by inhalation of TRPM8 agonists l-menthol and WS-12.Journal of applied physiology (Bethesda, Md. : 1985) · 2023Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The stereoisomers of menthol elicit cooling sensation to various levels. Though the high-resolution three-dimensional structures of the menthol receptor, the transient receptor potential melastatin 8 (TRPM8) ion channels, have been revolved in different states, the menthol-bound state structure is not determined and how the stereoisomers of menthol interact with TRPM8 remains largely elusive. Taking advantage of the identical atom composition but distinct spatial orientation of chemical groups in menthol stereoisomers, we performed thermodynamic mutant cycle analysis (TMCA) with patch-clamp recordings to probe the interaction between these ligands and TRPM8. By comparing (-)-menthol with (+)-neoisomenthol or (+)-neomenthol, we observed that the isopropyl or hydroxyl group in menthol interacts with the S4 or S3 helix in TRPM8, respectively. These interactions were also corroborated in our molecular docking of the stereoisomers, though the predicted structural details in the interactions of these ligands with TRPM8 residues are different. Therefore, we suggest similar molecular mechanisms of TRPM8 activation by the stereoisomers of menthol, while the binding configuration of an individual stereoisomer is varied.
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