ArticleeLife2016
Definition of two agonist types at the mammalian cold-activated channel TRPM8.
Article in eLife, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 35 citations in OpenAlex.
- Molecular basis for cold and menthol sensing by mammalian TRPM8.Nature communications · 2026Article
- Temperature-Dependent Menthol Binding across TRPM8 Conformational States.Journal of the American Chemical Society · 2026Article
- Cooling sensation biosensor coupled with the Chou-Talalay method for quantitative assessment of interaction patterns in binary cooling agent mixtures.Current research in food science · 2026Article
- Transduction Mechanisms for Cold Temperature in Mouse Trigeminal and Vagal Ganglion Neurons Innervating Different Peripheral Organs.Acta physiologica (Oxford, England) · 2025Article
- Direct modulation of TRPM8 ion channels by rapamycin and analog macrolide immunosuppressants.eLife · 2025Article
- Mechanisms of sensory adaptation and inhibition of the cold and menthol receptor TRPM8.Science advances · 2024Article
- Anti-Nociceptive Effects of Sphingomyelinase and Methyl-Beta-Cyclodextrin in the Icilin-Induced Mouse Pain Model.International journal of molecular sciences · 2024Article
- Molecular determinants of TRPM8 function: key clues for a cool modulation.Frontiers in pharmacology · 2023Review
- Activation mechanism of the mouse cold-sensing TRPM8 channel by cooling agonist and PIPScience (New York, N.Y.) · 2022Article
- TRPM8 Channels: Advances in Structural Studies and Pharmacological Modulation.International journal of molecular sciences · 2021Review
- Suppressive Effects of Transient Receptor Potential Melastatin 8 Agonist on Epileptiform Discharges and Epileptic Seizures.Frontiers in pharmacology · 2021Article
- Vascular Dysfunction in Diabetes and Obesity: Focus on TRP Channels.Frontiers in physiology · 2021Review
- Transcriptional Programming of Human Mechanosensory Neuron Subtypes from Pluripotent Stem Cells.Cell reports · 2020Article
- Recent Progress in TRPM8 Modulation: An Update.International journal of molecular sciences · 2019Review
- A critical evaluation of TRPA1-mediated locomotor behavior in zebrafish as a screening tool for novel anti-nociceptive drug discovery.Scientific reports · 2019Article
- The Immunosuppressant Macrolide Tacrolimus Activates Cold-Sensing TRPM8 Channels.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Suppressive Effects of Cooling Compounds Icilin on Penicillin G-Induced Epileptiform Discharges in Anesthetized Rats.Frontiers in pharmacology · 2019Article
- Human local adaptation of the TRPM8 cold receptor along a latitudinal cline.PLoS genetics · 2018Article
- The bovine TRPV3 as a pathway for the uptake of NaPloS one · 2018Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Various TRP channels act as polymodal sensors of thermal and chemical stimuli, but the mechanisms whereby chemical ligands impact on TRP channel gating are poorly understood. Here we show that AITC (allyl isothiocyanate; mustard oil) and menthol represent two distinct types of ligands at the mammalian cold sensor TRPM8. Kinetic analysis of channel gating revealed that AITC acts by destabilizing the closed channel, whereas menthol stabilizes the open channel, relative to the transition state. Based on these differences, we classify agonists as either type I (menthol-like) or type II (AITC-like), and provide a kinetic model that faithfully reproduces their differential effects. We further demonstrate that type I and type II agonists have a distinct impact on TRPM8 currents and TRPM8-mediated calcium signals in excitable cells. These findings provide a theoretical framework for understanding the differential actions of TRP channel ligands, with important ramifications for TRP channel structure-function analysis and pharmacology.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.