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Characterization of the mouse cold‐menthol receptor TRPM8 and vanilloid receptor type‐1 VR1 using a fluorometric imaging plate reader (FLIPR) assay
Open accessAbstract
TRPM8 (CMR1) is a Ca 2+‐permeable channel, which can be activated by low temperatures, menthol, eucalyptol and icilin. It belongs to the transient receptor potential (TRP) family, and therefore is related to vanilloid receptor type‐1 (VR1, TRPV1). We tested whether substances which are structurally related to menthol, or which produce a cooling sensation, could activate TRPM8, and compared the responses of TRPM8 and VR1 to these ligands. The effects of 70 odorants and menthol‐related substances on recombinant mouse TRPM8 (mTRPM8), expressed in HEK293 cells, were examined using a FLIPR® assay. In all, 10 substances (linalool, geraniol, hydroxycitronellal, WS‐3, WS‐23, FrescolatMGA, FrescolatML, PMD38, CoolactP and Cooling Agent 10) were found to be agonists. The EC 50 values of the agonists defined their relative potencies: icilin (0.2±0.1 μM)>FrescolatML (3.3±1.5 μM) > WS‐3 (3.7±1.7 μM) >(−)menthol (4.1±1.3 μM) >frescolatMAG (4.8±1.1 μM) > cooling agent 10 (6±2.2 μM) >(+)menthol (14.4±1.3 μM) > PMD38 (31±1.1 μM) > WS‐23 (44±7.3 μM) > Coolact P (66±20 μM) > geraniol (5.9±1.6 m M) > linalool (6.7±2.0 m M) > eucalyptol (7.7±2.0 m M) > hydroxycitronellal (19.6±2.2 m M). Known VR1 antagonists (BCTC, thio‐BCTC and capsazepine) were also able to block the response of TRPM8 to menthol (IC 50: 0.8±1.0, 3.5±1.1 and 18±1.1 μM, respectively). The Ca 2+ response of hVR1‐transfected HEK293 cells to the endogenous VR1 agonist N‐arachidonoyl‐dopamine was potentiated by low pH. In contrast, menthol‐ and icilin‐activated TRPM8 currents were suppressed by low pH. In conclusion, in the present study, we identified 10 new agonists and three antagonists of TRPM8. We found that, in contrast to VR1, TRPM8 is inhibited rather than potentiated by protons. British Journal of Pharmacology (2004) 141, 737–745. doi:10.1038/sj.bjp.0705652
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Cited by
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Dhaka, A., Viswanath, V., & Patapoutian, A. (2006) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.29.051605.112958 · Cited by 782
The transient receptor potential vanilloid-1 channel in thermoregulation: a thermosensor it is not
Romanovsky, A. A., Almeida, M. C., Garami, A., Steiner, A. A., Norman, M. H., Morrison, S. F., Nakamura, K., Burmeister, J. J., & Nucci, T. B. (2009) · Pharmacological Reviews · doi:10.1124/pr.109.001263 · Cited by 253
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Viana, F. (2011) · ACS Chemical Neuroscience · doi:10.1021/cn100102c · Cited by 196
Metadata
- Authors
- Behrendt, H., Germann, T., Gillen, C., Hatt, H., & Jostock, R.
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 2004-02
- Volume
- 141
- Issue
- 4
- Pages
- 737-745
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- OpenAlex
- W2166797811
- Cited by
- 458
- References
- 0
- FWCI
- 9.61
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Behrendt, H., Germann, T., Gillen, C., Hatt, H., & Jostock, R. (2004). Characterization of the mouse cold‐menthol receptor TRPM8 and vanilloid receptor type‐1 VR1 using a fluorometric imaging plate reader (FLIPR) assay. British Journal of Pharmacology. https://doi.org/10.1038/sj.bjp.0705652
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