TRPM8

Synonyms

Transient receptor potential cation channel subfamily M member 8, Transient receptor potential p8, TRPM8, LTrpC-6, Trp-P8, TRPP8, Transient Receptor Potential Cation Channel, Subfamily M, Member 8, Transient Receptor Potential Subfamily M Member 8, Long Transient Receptor Potential Channel 6, TRPM8 Cationic Channel, LTrpC6

Description

TRPM8 involved in receptor-activated non-selective cation channel involved in detection of sensations such as coolness, by being activated by cold temperature below 25 degrees Celsius. It is activated by icilin, eucalyptol, menthol, cold and modulation of intracellular pH. It is permeable for monovalent cations sodium, potassium, and cesium and divalent cation calcium. Temperature sensing is tightly linked to voltage-dependent gating. Activated upon depolarization, changes in temperature resulting in graded shifts of its voltage-dependent activation curves. The chemical agonist menthol functions as a gating modifier, shifting activation curves towards physiological membrane potentials. Temperature sensitivity arises from a tenfold difference in the activation energies associated with voltage-dependent opening and closing. In prostate cancer cells, shows strong inward rectification and high calcium selectivity in contrast to its behavior in normal cells which is characterized by outward rectification and poor cationic selectivity.

KO Status

RenMab: F1 (+/-)

Drug Information

Launched drugs: 7
Drugs in clinical trials: 6
Latest Research Phase: Approved

Drug Name

Code

Phase

Company

Indications

Clinical Trials

Menthol

Approved

Stomach Neoplasms, Prostatic Neoplasms, Castration-Resistant, Bronchitis, Sinusitis, Diagnostic agents, Pharyngitis

Menthol/Methyl Salicylate

Approved

Hisamitsu Pharmaceutical Co Inc

Pain

Bifonazole/Crotamiton/Lidocaine/Glycyrrhetinic Acid/Levomenthol

Approved

Tinea Pedis, Tinea

Methyl Salicylate/Menthol/camphor/Chlorphenamine Maleate

Approved

Ibuprofen/Levomenthol

Approved

Lidocaine Hydrochloride/Menthol

Approved

Anesthesia

2-Trichloromethyl-2-Propanol/Benzocaine/Chlorhexidine Acetate/Menthol

Approved

Anesthesia

AR-15512

AR-15512

Phase 2 Clinical

Aerie Pharmaceuticals

Dry Eye Syndromes

NRX-325008

NRX-325008

Phase 2 Clinical

Neurocentrx Pharma

Pain

Levomenthol

NPO-13

Phase 2 Clinical

University Hospitals Cleveland Medical Center

Colonic Neoplasms, Colonic Polyps, Intestinal Diseases

References


Title

Authors

Source

Identification of an HLA-A*0201-restricted T-cell epitope derived from the prostate cancer-associated protein trp-p8

Kiessling A., Fuessel S., Schmitz M., Stevanovic S., Meye A., Weigle B., Klenk U., Wirth M.P., Rieber E.P.,

Prostate 56:270-279(2003)

The principle of temperature-dependent gating in cold- and heat-sensitive TRP channels

Voets T., Droogmans G., Wissenbach U., Janssens A., Flockerzi V., Nilius B.,

Nature 430:748-754(2004)

Trafficking and assembly of the cold-sensitive TRPM8 channel

Erler I., Al-Ansary D.M., Wissenbach U., Wagner T.F., Flockerzi V., Niemeyer B.A.,

J. Biol. Chem. 281:38396-38404(2006)

TRP channel-associated factors are a novel protein family that regulates TRPM8 trafficking and activity

Gkika D., Lemonnier L., Shapovalov G., Gordienko D., Poux C., Bernardini M., Bokhobza A., Bidaux G., Degerny C., Verreman K., Guarmit B., Benahmed M., de Launoit Y., Bindels R.J., Fiorio Pla A., Prevarskaya N.,

J. Cell Biol. 208:89-107(2015)

Trp-p8, a novel prostate-specific gene, is up-regulated in prostate cancer and other malignancies and shares high homology with transient receptor potential calcium channel proteins

Tsavaler L., Shapero M.H., Morkowski S., Laus R.,

Cancer Res. 61:3760-3769(2001)

Novel role of cold/menthol-sensitive transient receptor potential melastatine family member 8 (TRPM8) in the activation of store-operated channels in LNCaP human prostate cancer epithelial cells

Thebault S., Lemonnier L., Bidaux G., Flourakis M., Bavencoffe A., Gordienko D., Roudbaraki M., Delcourt P., Panchin Y., Shuba Y., Skryma R., Prevarskaya N.,

J. Biol. Chem. 280:39423-39435(2005)

Regulation of activity of transient receptor potential melastatin 8 (TRPM8) channel by its short isoforms

Bidaux G., Beck B., Zholos A., Gordienko D., Lemonnier L., Flourakis M., Roudbaraki M., Borowiec A.S., Fernandez J., Delcourt P., Lepage G., Shuba Y., Skryma R., Prevarskaya N.,

J. Biol. Chem. 287:2948-2962(2012)

Generation and annotation of the DNA sequences of human chromosomes 2 and 4

Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H., Wilson R.K.,

Nature 434:724-731(2005)

The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)

The MGC Project Team,

Genome Res. 14:2121-2127(2004)