Top ▲

TRPM8

Click here for help

Target not currently curated in GtoImmuPdb

Target id: 500

Nomenclature: TRPM8

Family: Transient Receptor Potential channels (TRP)

Contents:

Gene and Protein Information Click here for help
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1 1104 2q37.1 TRPM8 transient receptor potential cation channel subfamily M member 8 28
Mouse 6 1 1104 1 D Trpm8 transient receptor potential cation channel, subfamily M, member 8 21
Rat 6 1 1104 9q35 Trpm8 transient receptor potential cation channel, subfamily M, member 8 17
Previous and Unofficial Names Click here for help
LTrpC6 | CMR1 | cold/menthol receptor 1 | transient receptor potential cation channel
Database Links Click here for help
Alphafold Q7Z2W7 (Hs), Q8R4D5 (Mm), Q8R455 (Rn)
ChEMBL Target CHEMBL1075319 (Hs), CHEMBL3108632 (Mm), CHEMBL5011 (Rn)
DrugBank Target Q7Z2W7 (Hs)
Ensembl Gene ENSG00000144481 (Hs), ENSMUSG00000036251 (Mm), ENSRNOG00000019035 (Rn)
Entrez Gene 79054 (Hs), 171382 (Mm), 171384 (Rn)
Human Protein Atlas ENSG00000144481 (Hs)
KEGG Gene hsa:79054 (Hs), mmu:171382 (Mm), rno:171384 (Rn)
OMIM 620053 (Hs)
Pharos Q7Z2W7 (Hs)
RefSeq Nucleotide NM_024080 (Hs), NM_134252 (Mm), NM_134371 (Rn)
RefSeq Protein NP_076985 (Hs), NP_599013 (Mm), NP_599198 (Rn)
UniProtKB Q7Z2W7 (Hs), Q8R4D5 (Mm), Q8R455 (Rn)
Wikipedia TRPM8 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Structure of the cold- and menthol-sensing ion channel TRPM8
PDB Id:  6BPQ
Resolution:  4.1Å
Species:  Human
References:  31
Associated Proteins Click here for help
Heteromeric Pore-forming Subunits
Name References
Not determined
Auxiliary Subunits
Name References
Not determined
Other Associated Proteins
Name References
Gq-alpha 33
Functional Characteristics Click here for help
γ = 40-83 pS at positive potentials; conducts mono- and di-valent cations non-selectively (PCa/PNa = 1.0–3.3); pronounced outward rectification; demonstrates densensitization to chemical agonists and adaptation to a cold stimulus in the presence of Ca2+; modulated by lysophospholipids and PUFAs
Ion Selectivity and Conductance Click here for help
Species:  Mouse
Rank order:  Cs+ > K+ > Na+
References:  21
Species:  Rat
Rank order:  Ca2+ [83.0 pS] > K+ = Na+ = Cs+ [42.0 pS]
References:  12,17,32
Ion Selectivity and Conductance Comments
Single channel conductance (rat) = 83 pS [17]
PCa:PNa ratio = 0.97-3.3 [17,21]
Voltage Dependence Click here for help
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -10.0 – 80.0 - 7 HEK 293 cells transiently transfected with rTrpm8. Rat
Inactivation  - -
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  25.0 – 200.0 1.0 – 15.0 30 HEK 293 cells transiently transfected with TRPM8. Human
Inactivation  - -
Comments  TRPM8 is weakly voltage dependent.
Chemical activators (Human)
agonist activities are temperature dependent and potentiated by cooling
Physical activators (Human)
depolarization (V½ ~ +50 mV at 15°C), cooling (< 22-26°C)

Download all structure-activity data for this target as a CSV file go icon to follow link

Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
icilin Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Mm Agonist 6.7 – 6.9 pEC50 - Physiological 2,6
⤷ pEC50 6.7 – 6.9 (EC50 1.99x10-7 – 1.25x10-7 M) [2,6]
Holding voltage: Physiological
icilin Small molecule or natural product Ligand has a PDB structure Rn Full agonist 6.4 pEC50 - Physiological 17-18,21
⤷ pEC50 6.4 Icilin activation is Ca2+-dependent. [17-18,21]
Holding voltage: Physiological
Description: Whole-cell voltage-clamp recordings or Ca2+-microfluorimetry in heterologous cells (HEK, CHO, and Xenopus oocytes) expressing TRPM8.
frescolat ML Small molecule or natural product Mm Partial agonist 5.5 pEC50 - Physiological 6
⤷ pEC50 5.5 [6]
Holding voltage: Physiological
WS-3 Small molecule or natural product Mm Partial agonist 5.4 pEC50 - Physiological 6
⤷ pEC50 5.4 [6]
Holding voltage: Physiological
frescolat MGA Small molecule or natural product Mm Partial agonist 5.3 pEC50 - Physiological 6
⤷ pEC50 5.3 [6]
Holding voltage: Physiological
cooling agent 10 Small molecule or natural product Mm Partial agonist 5.2 pEC50 - Physiological 6
⤷ pEC50 5.2 [6]
Holding voltage: Physiological
WS-12 Small molecule or natural product Ligand has a PDB structure Rn Full agonist 4.9 pEC50 - Physiological 15,25
⤷ pEC50 4.9 (EC50 1.25x10-5 M) [15,25]
Holding voltage: Physiological
Description: Whole-cell voltage-clamp recordings or Ca2+-microfluorimetry in heterologous cells (HEK, CHO, and Xenopus oocytes) expressing TRPM8
tacrolimus Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Agonist 4.8 pEC50 - - 4
⤷ pEC50 4.8 (EC50 1.41x10-5 M) [4]
Description: FURA2AM experiments, human TRPM8
(+)-menthol Small molecule or natural product Mm Partial agonist 4.8 pEC50 - Physiological 6
⤷ pEC50 4.8 [6]
Holding voltage: Physiological
(-)-menthol Small molecule or natural product Approved drug Click here for species-specific activity table Mm Partial agonist 4.0 – 5.4 pEC50 - Physiological 2,6
⤷ pEC50 4.0 – 5.4 [2,6]
Holding voltage: Physiological
(-)-menthol Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs - 4.6 pEC50 - -120.0 – 160.0 30
⤷ pEC50 4.6 (EC50 2.51x10-5 M) inhibited by intracellular Ca2+ [30]
Holding voltage: -120.0 – 160.0 mV
WS-5 Small molecule or natural product Rn Full agonist 4.6 pEC50 - Physiological 25
⤷ pEC50 4.6 [25]
Holding voltage: Physiological
Description: Whole-cell voltage-clamp recordings or Ca2+-microfluorimetry in heterologous cells (HEK, CHO, and Xenopus oocytes) expressing TRPM8
PMD38 Small molecule or natural product Mm Partial agonist 4.5 pEC50 - Physiological 6
⤷ pEC50 4.5 [6]
Holding voltage: Physiological
CPS125 Small molecule or natural product Rn Full agonist 4.5 pEC50 - Physiological 25
⤷ pEC50 4.5 [25]
Holding voltage: Physiological
Description: Whole-cell voltage-clamp recordings or Ca2+<.sup>-microfluorimetry in heterologous cells (HEK, CHO, and Xenopus oocytes) expressing TRPM8
WS-23 Small molecule or natural product Mm Partial agonist 4.4 pEC50 - Physiological 6
⤷ pEC50 4.4 [6]
Holding voltage: Physiological
isopulegol Small molecule or natural product Mm Partial agonist 4.2 pEC50 - Physiological 6
⤷ pEC50 4.2 [6]
Holding voltage: Physiological
(-)-menthol Small molecule or natural product Approved drug Rn Partial agonist 4.1 – 4.2 pEC50 - -60.0 17
⤷ pEC50 4.1 – 4.2 [17]
Holding voltage: -60.0 mV
frescolat ML Small molecule or natural product Rn Full agonist 3.8 pEC50 - Physiological 6,25
⤷ pEC50 3.8 [6,25]
Holding voltage: Physiological
Description: Whole-cell voltage-clamp recordings or Ca2+-microfluorimetry in heterologous cells (HEK, CHO, and Xenopus oocytes) expressing TRPM8
eucalyptol Small molecule or natural product Rn Partial agonist 2.5 pEC50 - -60.0 17
⤷ pEC50 2.5 [17]
Holding voltage: -60.0 mV
geraniol Small molecule or natural product Ligand has a PDB structure Mm Partial agonist 2.2 pEC50 - Physiological 6
⤷ pEC50 2.2 [6]
Holding voltage: Physiological
linalool Small molecule or natural product Mm Partial agonist 2.2 pEC50 - Physiological 6
⤷ pEC50 2.2 [6]
Holding voltage: Physiological
eucalyptol Small molecule or natural product Mm Partial agonist 2.1 pEC50 - Physiological 6
⤷ pEC50 2.1 [6]
Holding voltage: Physiological
hydroxycitronellal Small molecule or natural product Mm Partial agonist 1.7 pEC50 - Physiological 6
⤷ pEC50 1.7 [6]
Holding voltage: Physiological
View species-specific activator tables
Activator Comments
Cold temperatures below 26°C activate TRPM8 and agonists shift the temperature sensitivity of the channel towards warmer temperatures [17]. Channel activation requires the presence of the phospholipid PIP2 in the membrane [23]. Icilin requires Ca2+ as a co-factor for full agonist activity.
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
elismetrep Small molecule or natural product Hs Antagonist 9.1 pIC50 29
⤷ pIC50 9.1 (IC50 9x10-10 M) [29]
Description: Inhibition of menthol-induced intracellular calcium mobilisation using HEK293 cells stably expressing hTRPM8.
KPR-5714 Small molecule or natural product Hs Antagonist 7.6 pIC50 19
⤷ pIC50 7.6 (IC50 2.53x10-8 M) [19]
cannabigerol Small molecule or natural product Rn Antagonist - - 22
⤷ [22]
Description: Antagonism of icilin-induced elevation of intracellular calcium level in HEK293 cells expressing rat TRPM8.
Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
PBMC Small molecule or natural product Rn Inhibition 9.3 pIC50 - Physiological 13
⤷ pIC50 9.3 (IC50 5x10-10 M) [13]
Holding voltage: Physiological
Description: Whole-cell voltage-clamp recordings or Ca2+-microfluorimetry in heterologous cells (HEK) expressing TRPM8
M8-B Small molecule or natural product Rn Pore blocker 7.2 – 8.1 pIC50 - Physiological 1
⤷ pIC50 7.2 – 8.1 (IC50 6.43x10-8 – 7.8x10-9 M) Inhibited activation by cold (IC50 = 7.8nM); icilin (IC50 = 26.9nM), or menthol (IC50 = 64.3nM) in a concentration-dependent manner. [1]
Holding voltage: Physiological
PF-05105679 Small molecule or natural product Hs Antagonist 7.0 pIC50 - - 3
⤷ pIC50 7.0 (IC50 1.03x10-7 M) [3]
BCTC Small molecule or natural product Mm Antagonist 6.1 pIC50 - Physiological 6
⤷ pIC50 6.1 (IC50 8x10-7 M) [6]
Holding voltage: Physiological
Description: Whole-cell voltage-clamp recordings or Ca2+-microfluorimetry in heterologous cells (HEK, CHO, and Xenopus oocytes) expressing TRPM8
scutellarein Small molecule or natural product Click here for species-specific activity table Hs - 5.8 pIC50 - - 24
⤷ pIC50 5.8 (IC50 1.7x10-6 M) [24]
thio-BCTC Small molecule or natural product Mm Antagonist 5.5 pIC50 - Physiological 6
⤷ pIC50 5.5 [6]
Holding voltage: Physiological
thio-BCTC Small molecule or natural product Rn Inhibition 5.5 pIC50 - Physiological 6,16
⤷ pIC50 5.5 [6,16]
Holding voltage: Physiological
Description: Whole-cell voltage-clamp recordings or Ca2+-microfluorimetry in heterologous cells (HEK) expressing TRPM8
2-APB Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Mm Antagonist 4.9 – 5.1 pIC50 - 100.0 – -100.0 11,20
⤷ pIC50 4.9 – 5.1 [11,20]
Holding voltage: 100.0 – -100.0 mV
capsazepine Small molecule or natural product Ligand has a PDB structure Mm Antagonist 4.7 pIC50 - Physiological 6
⤷ pIC50 4.7 (IC50 1.8x10-5 M) [6]
Holding voltage: Physiological
5-benzyloxytryptamine Small molecule or natural product Hs - - - - -
⤷
linoleic acid Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs - - - - -
⤷
clotrimazole Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs - - - - -
⤷
anandamide Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs - - - - -
⤷
Δ9-tetrahydrocannabinol Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs - - - - -
⤷
La3+ Click here for species-specific activity table Hs - - - - -
⤷
ACAA Small molecule or natural product Click here for species-specific activity table Hs - - - - -
⤷
AMTB Small molecule or natural product Ligand has a PDB structure Hs - - - - - 14
⤷ [14]
cannabidiol Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs - - - - -
⤷
NADA Small molecule or natural product Click here for species-specific activity table Hs - - - - -
⤷
View species-specific channel blocker tables
Channel Blocker Comments
Compound M8-B has similar IC50 at the human TRPM8 expressed in CHO cells [1], and also shows inhibitory activity at mouse Trpm8 in a subset of primary somatosensory neurons [1]. It is unknown whether M8-B functions as a pore blocker or a gating inhibitor.
Tissue Distribution Click here for help
Prostate
Species:  Human
Technique:  Northern Blot
References:  28
Prostate, testis, bladder > breast, thymus
Species:  Human
Technique:  RT-PCR
References:  28
Prostate, breast
Species:  Human
Technique:  In situ hybridisation
References:  28
Dorsal root ganglion
Species:  Mouse
Technique:  Northern Blot
References:  21
Dorsal root ganglion, trigeminal ganglion
Species:  Mouse
Technique:  In situ hybridisation
References:  21
Dorsal root ganglia, trigeminal ganglia
Species:  Rat
Technique:  Northern Blot
References:  17
Dorsal root ganglia, trigeminal ganglia
Species:  Rat
Technique:  In situ hybridisation
References:  17
Dorsal root ganglion, testis, prostate, bladder
Species:  Rat
Technique:  RT-PCR
References:  26
Tissue Distribution Comments
Genetically targeted reporter proteins (GFP-tagged) have been expressed via the Trmp8 promoter as an alternative means to examine putative channel expression [9,27].
Functional Assays Click here for help
Patch-clamp analysis (whole-cell and single-channel recordings), intracellular Ca2+ imaging.
Species:  Rat
Tissue:  HEK cells transfected with a TRPM8 vector
Response measured:  Activation by cold, menthol icilin etc.
References:  17
Patch-clamp analysis (whole-cell and single-channel recordings), intracellular Ca2+ imaging.
Species:  Mouse
Tissue:  CHO cells transfected with a TRPM8 containing vector and Xenopus ooctyes injected with TRPM8 cRNA.
Response measured:  Activation by cold, menthol, and icilin
References:  21
Patch-clamp analysis (whole-cell and single-channel recordings).
Species:  Human
Tissue:  HEK cells transfected with a TRPM8 containing vector.
Response measured:  Activation by cold and menthol
References:  30
Patch-clamp analysis (whole-cell and single-channel recordings), intracellular Ca2+ imaging.
Species:  Rat
Tissue:  HEK cells transfected with a TRPM8 containing vector and xXenopus ooctyes injected with TRPM8 cRNA.
Response measured:  Activation by cold, menthol, and icilin
References:  17
Single channel recordings in planar lipid bilayers
Species:  Rat
Tissue:  Purified TRPM8 channels reconstituted into planar lipid bilayers
Response measured:  Activation by menthol
References:  32
Physiological Functions Click here for help
A cold and cold-mimetic chemical receptor used for the detection of external stimuli.
Species:  Mouse
Tissue:  Dorsal root and trigeminal ganglia, as well as other sensory ganglia innervating internal tissues.
References:  5,8,10,17,21
Physiological Functions Comments
The physiological functions described are also found in rats, humans, avians, and amphibians.
Physiological Consequences of Altering Gene Expression Click here for help
TRPM8-knockout mice have deficits in cold perception as determined by several behavioral assays.
Species:  Mouse
Tissue:  Sensory ganglia
Technique:  Gene targeting by homologous recombination
References:  5,8,10
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

Show »

Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Trpm8tm1Lex Trpm8tm1Lex/Trpm8tm1Lex
involves: 129S5/SvEvBrd * C57BL/6		 MGI:2181435  MP:0004811 abnormal neuron physiology PMID: 17481392 
Trpm8tm1Apat Trpm8tm1Apat/Trpm8tm1Apat
involves: 129S1/Sv * C57BL/6		 MGI:2181435  MP:0004811 abnormal neuron physiology PMID: 17481391 
Trpm8tm1Lex Trpm8tm1Lex/Trpm8tm1Lex
involves: 129S5/SvEvBrd * C57BL/6		 MGI:2181435  MP:0002736 abnormal nociception after inflammation PMID: 17481392 
Trpm8tm1Apat Trpm8tm1Apat/Trpm8tm1Apat
involves: 129S1/Sv * C57BL/6		 MGI:2181435  MP:0002736 abnormal nociception after inflammation PMID: 17481391 
Trpm8tm1Lex Trpm8tm1Lex/Trpm8tm1Lex
involves: 129S5/SvEvBrd * C57BL/6		 MGI:2181435  MP:0001970 abnormal pain threshold PMID: 17481392 
Trpm8tm1Jul Trpm8tm1Jul/Trpm8tm1Jul
involves: 129P2/OlaHsd * C57BL/6		 MGI:2181435  MP:0003663 abnormal thermosensation PMID: 17538622 
Trpm8tm1Lex Trpm8tm1Lex/Trpm8tm1Lex
involves: 129S5/SvEvBrd * C57BL/6		 MGI:2181435  MP:0003663 abnormal thermosensation PMID: 17481392 
Trpm8tm1Apat Trpm8tm1Apat/Trpm8tm1Apat
involves: 129S1/Sv * C57BL/6		 MGI:2181435  MP:0003663 abnormal thermosensation PMID: 17481391 
Trpm8tm1Jul Trpm8tm1Jul/Trpm8tm1Jul
involves: 129P2/OlaHsd * C57BL/6		 MGI:2181435  MP:0001973 increased thermal nociceptive threshold PMID: 17538622 
Trpm8tm1Lex Trpm8tm1Lex/Trpm8tm1Lex
involves: 129S5/SvEvBrd * C57BL/6		 MGI:2181435  MP:0001973 increased thermal nociceptive threshold PMID: 17481392 
Trpm8tm1Apat Trpm8tm1Apat/Trpm8tm1Apat
involves: 129S1/Sv * C57BL/6		 MGI:2181435  MP:0001973 increased thermal nociceptive threshold PMID: 17481391 
Gene Expression and Pathophysiology Click here for help
Up-regulated in adenocarcinomas.
Tissue or cell type:  Prostate as well as breast, colon, lung and skin
Pathophysiology:  Adenocarcinoma
Species:  Human
Technique:  In-situ hybridisation
References:  28

References

Show »

1. Almeida MC, Hew-Butler T, Soriano RN, Rao S, Wang W, Wang J, Tamayo N, Oliveira DL, Nucci TB, Aryal P et al.. (2012) Pharmacological blockade of the cold receptor TRPM8 attenuates autonomic and behavioral cold defenses and decreases deep body temperature. J Neurosci, 32 (6): 2086-99. [PMID:22323721]

2. Andersson DA, Chase HW, Bevan S. (2004) TRPM8 activation by menthol, icilin, and cold is differentially modulated by intracellular pH. J Neurosci, 24 (23): 5364-9. [PMID:15190109]

3. Andrews MD, Af Forselles K, Beaumont K, Galan SR, Glossop PA, Grenie M, Jessiman A, Kenyon AS, Lunn G, Maw G et al.. (2015) Discovery of a Selective TRPM8 Antagonist with Clinical Efficacy in Cold-Related Pain. ACS Med Chem Lett, 6 (4): 419-24. [PMID:25893043]

4. Arcas JM, González A, Gers-Barlag K, González-González O, Bech F, Demirkhanyan L, Zakharian E, Belmonte C, Gomis A, Viana F. (2019) The Immunosuppressant Macrolide Tacrolimus Activates Cold-Sensing TRPM8 Channels. J Neurosci, 39 (6): 949-969. [PMID:30545944]

5. Bautista DM, Siemens J, Glazer JM, Tsuruda PR, Basbaum AI, Stucky CL, Jordt SE, Julius D. (2007) The menthol receptor TRPM8 is the principal detector of environmental cold. Nature, 448 (7150): 204-8. [PMID:17538622]

6. Behrendt HJ, 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. Br J Pharmacol, 141 (4): 737-45. [PMID:14757700]

7. Brauchi S, Orio P, Latorre R. (2004) Clues to understanding cold sensation: thermodynamics and electrophysiological analysis of the cold receptor TRPM8. Proc Natl Acad Sci USA, 101 (43): 15494-9. [PMID:15492228]

8. Colburn RW, Lubin ML, Stone DJ, Wang Y, Lawrence D, D'Andrea MR, Brandt MR, Liu Y, Flores CM, Qin N. (2007) Attenuated cold sensitivity in TRPM8 null mice. Neuron, 54 (3): 379-86. [PMID:17481392]

9. Dhaka A, Earley TJ, Watson J, Patapoutian A. (2008) Visualizing cold spots: TRPM8-expressing sensory neurons and their projections. J Neurosci, 28 (3): 566-75. [PMID:18199758]

10. Dhaka A, Murray AN, Mathur J, Earley TJ, Petrus MJ, Patapoutian A. (2007) TRPM8 is required for cold sensation in mice. Neuron, 54 (3): 371-8. [PMID:17481391]

11. Hu HZ, Gu Q, Wang C, Colton CK, Tang J, Kinoshita-Kawada M, Lee LY, Wood JD, Zhu MX. (2004) 2-aminoethoxydiphenyl borate is a common activator of TRPV1, TRPV2, and TRPV3. J Biol Chem, 279 (34): 35741-8. [PMID:15194687]

12. Hui K, Guo Y, Feng ZP. (2005) Biophysical properties of menthol-activated cold receptor TRPM8 channels. Biochem Biophys Res Commun, 333 (2): 374-82. [PMID:15950184]

13. Knowlton WM, Daniels RL, Palkar R, McCoy DD, McKemy DD. (2011) Pharmacological blockade of TRPM8 ion channels alters cold and cold pain responses in mice. PLoS ONE, 6 (9): e25894. [PMID:21984952]

14. Lashinger ES, Steiginga MS, Hieble JP, Leon LA, Gardner SD, Nagilla R, Davenport EA, Hoffman BE, Laping NJ, Su X. (2008) AMTB, a TRPM8 channel blocker: evidence in rats for activity in overactive bladder and painful bladder syndrome. Am J Physiol Renal Physiol, 295 (3): F803-10. [PMID:18562636]

15. Ma S, G G, Ak VE, Jf D, H H. (2008) Menthol derivative WS-12 selectively activates transient receptor potential melastatin-8 (TRPM8) ion channels. Pak J Pharm Sci, 21 (4): 370-8. [PMID:18930858]

16. Madrid R, Donovan-Rodríguez T, Meseguer V, Acosta MC, Belmonte C, Viana F. (2006) Contribution of TRPM8 channels to cold transduction in primary sensory neurons and peripheral nerve terminals. J Neurosci, 26 (48): 12512-25. [PMID:17135413]

17. McKemy DD, Neuhausser WM, Julius D. (2002) Identification of a cold receptor reveals a general role for TRP channels in thermosensation. Nature, 416 (6876): 52-8. [PMID:11882888]

18. Myers BR, Sigal YM, Julius D. (2009) Evolution of thermal response properties in a cold-activated TRP channel. PLoS ONE, 4 (5): e5741. [PMID:19492038]

19. Nakanishi O, Fujimori Y, Aizawa N, Hayashi T, Matsuzawa A, Kobayashi JI, Hirasawa H, Mutai Y, Tanada F, Igawa Y. (2020) KPR-5714, a Novel Transient Receptor Potential Melastatin 8 Antagonist, Improves Overactive Bladder via Inhibition of Bladder Afferent Hyperactivity in Rats. J Pharmacol Exp Ther, 373 (2): 239-247. [PMID:32102918]

20. Naziroğlu M, Ozgül C. (2012) Effects of antagonists and heat on TRPM8 channel currents in dorsal root ganglion neuron activated by nociceptive cold stress and menthol. Neurochem Res, 37 (2): 314-20. [PMID:21964764]

21. Peier AM, Moqrich A, Hergarden AC, Reeve AJ, Andersson DA, Story GM, Earley TJ, Dragoni I, McIntyre P, Bevan S et al.. (2002) A TRP channel that senses cold stimuli and menthol. Cell, 108 (5): 705-15. [PMID:11893340]

22. Pollastro F, Taglialatela-Scafati O, Allarà M, Muñoz E, Di Marzo V, De Petrocellis L, Appendino G. (2011) Bioactive prenylogous cannabinoid from fiber hemp (Cannabis sativa). J Nat Prod, 74 (9): 2019-22. [PMID:21902175]

23. Rohács T, Lopes CM, Michailidis I, Logothetis DE. (2005) PI(4,5)P2 regulates the activation and desensitization of TRPM8 channels through the TRP domain. Nat Neurosci, 8 (5): 626-34. [PMID:15852009]

24. Sanechika S, Shimobori C, Ohbuchi K. (2021) Identification of herbal components as TRPA1 agonists and TRPM8 antagonists. J Nat Med, 75 (3): 717-725. [PMID:33877504]

25. Sherkheli MA, Vogt-Eisele AK, Bura D, Beltrán Márques LR, Gisselmann G, Hatt H. (2010) Characterization of selective TRPM8 ligands and their structure activity response (S.A.R) relationship. J Pharm Pharm Sci, 13 (2): 242-53. [PMID:20816009]

26. Stein RJ, Santos S, Nagatomi J, Hayashi Y, Minnery BS, Xavier M, Patel AS, Nelson JB, Futrell WJ, Yoshimura N et al.. (2004) Cool (TRPM8) and hot (TRPV1) receptors in the bladder and male genital tract. J Urol, 172 (3): 1175-8. [PMID:15311065]

27. Takashima Y, Daniels RL, Knowlton W, Teng J, Liman ER, McKemy DD. (2007) Diversity in the neural circuitry of cold sensing revealed by genetic axonal labeling of transient receptor potential melastatin 8 neurons. J Neurosci, 27 (51): 14147-57. [PMID:18094254]

28. Tsavaler L, Shapero MH, Morkowski S, Laus R. (2001) 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. Cancer Res, 61 (9): 3760-9. [PMID:11325849]

29. Tsuzuki Y, Sawamoto D, Sakamoto T, Kato T, Niwa Y, Awai N. (2012) Sulfonamide compounds having trpm8 antagonistic activity. Patent number: WO2012124825. Assignee: Mitsubishi Tanabe Pharma Corporation. Priority date: 16/03/2011. Publication date: 20/09/2012.

30. Voets T, Droogmans G, Wissenbach U, Janssens A, Flockerzi V, Nilius B. (2004) The principle of temperature-dependent gating in cold- and heat-sensitive TRP channels. Nature, 430 (7001): 748-54. [PMID:15306801]

31. Yin Y, Wu M, Zubcevic L, Borschel WF, Lander GC, Lee SY. (2018) Structure of the cold- and menthol-sensing ion channel TRPM8. Science, 359 (6372): 237-241. [PMID:29217583]

32. Zakharian E, Thyagarajan B, French RJ, Pavlov E, Rohacs T. (2009) Inorganic polyphosphate modulates TRPM8 channels. PLoS ONE, 4 (4): e5404. [PMID:19404398]

33. Zhang X, Mak S, Li L, Parra A, Denlinger B, Belmonte C, McNaughton PA. (2012) Direct inhibition of the cold-activated TRPM8 ion channel by Gαq. Nat Cell Biol, 14 (8): 851-8. [PMID:22750945]

Contributors

Show »

How to cite this page