ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2019
The Immunosuppressant Macrolide Tacrolimus Activates Cold-Sensing TRPM8 Channels.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 50 citations in OpenAlex.
- Temperature-Dependent Menthol Binding across TRPM8 Conformational States.Journal of the American Chemical Society · 2026Article
- Molecular and neurovascular mechanisms of thermal sensitivity in teeth.Temperature (Austin, Tex.) · 2026Review
- Cold- and TRPM8-dependent shaking in mammals and birds.Communications biology · 2025Article
- Direct modulation of TRPM8 ion channels by rapamycin and analog macrolide immunosuppressants.eLife · 2025Article
- P2X4 Receptor Antagonist Ameliorates Ocular Pain in Rats After Lacrimal Gland Removal.Translational vision science & technology · 2025Article
- Loss of TRPM8 Exacerbate Herpes Simplex Keratitis Infection in Mice by Promoting the Infiltration of CD11b+ Ly6G+ Cells and Increasing the Viral Load in the Cornea.Investigative ophthalmology & visual science · 2023Article
- Quality-by-Design Approach for Investigating the Efficacy of Tacrolimus and Hyaluronic Acid-Loaded Ethosomal Gel in Dermal Management of Psoriasis: In Vitro, Ex Vivo, and In Vivo Evaluation.AAPS PharmSciTech · 2023Article
- Heterologous overproduction of oviedomycin by refactoring biosynthetic gene cluster and metabolic engineering of host strain Streptomyces coelicolor.Microbial cell factories · 2023Article
- Cyclosporine A Decreases Dryness-Induced Hyperexcitability of Corneal Cold-Sensitive Nerve Terminals.International journal of molecular sciences · 2023Article
- Consideration of the importance of measuring thermal discomfort in biomedical research.Trends in molecular medicine · 2023Review
- Ion channels in dry eye disease.Indian journal of ophthalmology · 2023Review
- Effect of TRPM8 Functional Loss on Corneal Epithelial Wound Healing in Mice.Investigative ophthalmology & visual science · 2023Article
- Mutations of TRPM8 channels: Unraveling the molecular basis of activation by cold and ligands.Medicinal research reviews · 2022Review
- Transient Receptor Potential Channels: Important Players in Ocular Pain and Dry Eye Disease.Pharmaceutics · 2022Review
- Impact of novel microbial secondary metabolites on the pharma industry.Applied microbiology and biotechnology · 2022Review
- Ocular Surface Ion-Channels Are Closely Related to Dry Eye: Key Research Focus on Innovative Drugs for Dry Eye.Frontiers in medicine · 2022Review
- TRPM8 Channels: Advances in Structural Studies and Pharmacological Modulation.International journal of molecular sciences · 2021Review
- CaCells · 2021Review
- Phenylalanine-Derived β-Lactam TRPM8 Modulators. Configuration Effect on the Antagonist Activity.International journal of molecular sciences · 2021Article
- Topical TRPM8 Agonist for Relieving Neuropathic Ocular Pain in Patients with Dry Eye: A Pilot Study.Journal of clinical medicine · 2021Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TRPM8 is a polymodal, nonselective cation channel activated by cold temperature and cooling agents that plays a critical role in the detection of environmental cold. We found that TRPM8 is a pharmacological target of tacrolimus (FK506), a macrolide immunosuppressant with several clinical uses, including the treatment of organ rejection following transplants, treatment of atopic dermatitis, and dry eye disease. Tacrolimus is an inhibitor of the phosphatase calcineurin, an action shared with cyclosporine. Tacrolimus activates TRPM8 channels in different species, including humans, and sensitizes their response to cold temperature by inducing a leftward shift in the voltage-dependent activation curve. The effects of tacrolimus on purified TRPM8 in lipid bilayers demonstrates conclusively that it has a direct gating effect. Moreover, the lack of effect of cyclosporine rules out the canonical signaling pathway involving the phosphatase calcineurin. Menthol (TRPM8-Y745H)- and icilin (TRPM8-N799A)-insensitive mutants were also activated by tacrolimus, suggesting a different binding site. In cultured mouse DRG neurons, tacrolimus evokes an increase in intracellular calcium almost exclusively in cold-sensitive neurons, and these responses were drastically blunted in
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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.