Complex Regulation of the TRPM8 Cold Receptor Channel: Role of Arachidonic Acid Release Following M3 Muscarinic Receptor Stimulation

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2011 Jan 20

PMID 21245133

Citations 10

Authors

Alexis Bavencoffe

Artem Kondratskyi

Dimitra Gkika

Brigitte Mauroy

Yaroslav Shuba

Natalia Prevarskaya

Roman Skryma

Affiliations

Soon will be listed here.

Abstract

Cold/menthol-activated TRPM8 (transient receptor potential channel melastatin member 8) is primarily expressed in sensory neurons, where it constitutes the principal receptor of environmental innocuous cold. TRPM8 has been shown to be regulated by multiple influences such as phosphorylation, pH, Ca(2+), and lipid messengers. One such messenger is arachidonic acid (AA), which has been shown to inhibit TRPM8 channel activity. However, the physiological pathways mediating the inhibitory effect of AA on TRPM8 still remain unknown. Here, we demonstrate that TRPM8 is regulated via M3 muscarinic acetylcholine receptor-coupled signaling cascade based on the activation of cytosolic phospholipase A2 (cPLA2) and cPLA2-catalyzed derivation of AA. Stimulation of M3 receptors heterologously co-expressed with TRPM8 in HEK-293 cells by nonselective muscarinic agonist, oxotremorine methiodide (Oxo-M), caused inhibition of TRPM8-mediated membrane current, which could be mimicked by AA and antagonized by pharmacological or siRNA-mediated cPLA2 silencing. Our results demonstrate the intracellular functional link between M3 receptor and TRPM8 channel via cPLA2/AA and suggest a novel physiological mechanism of arachidonate-mediated regulation of TRPM8 channel activity through muscarinic receptors. We also summarize the existing TRPM8 regulations and discuss their physiological and pathological significance.

Citing Articles

EMC3 is critical for CFTR function and calcium mobilization in the mouse intestinal epithelium.

Penrod S, Tang X, Moon C, Whitsett J, Naren A, Huang Y Am J Physiol Gastrointest Liver Physiol. 2024; 328(1):G72-G82.

PMID: 39641142 PMC: 11901349. DOI: 10.1152/ajpgi.00066.2024.

Bidirectional TRP/L Type Ca Channel/RyR/BK Molecular and Functional Signaloplex in Vascular Smooth Muscles.

Dryn D, Melnyk M, Melanaphy D, Kizub I, Johnson C, Zholos A Biomolecules. 2023; 13(5).

PMID: 37238629 PMC: 10216084. DOI: 10.3390/biom13050759.

Comprehensive Pan-Cancer Analysis of TRPM8 in Tumor Metabolism and Immune Escape.

Zhang W, Qiao X, Li Q, Cui C, Qiao C, Shen Y Front Oncol. 2022; 12:914060.

PMID: 35847920 PMC: 9281503. DOI: 10.3389/fonc.2022.914060.

Actions and Mechanisms of Polyunsaturated Fatty Acids on Voltage-Gated Ion Channels.

Elinder F, Liin S Front Physiol. 2017; 8:43.

PMID: 28220076 PMC: 5292575. DOI: 10.3389/fphys.2017.00043.

Ion channel mechanisms of rat tail artery contraction-relaxation by menthol involving, respectively, TRPM8 activation and L-type Ca2+ channel inhibition.

Melanaphy D, Johnson C, Kustov M, Watson C, Borysova L, Burdyga T Am J Physiol Heart Circ Physiol. 2016; 311(6):H1416-H1430.

PMID: 27765744 PMC: 5206336. DOI: 10.1152/ajpheart.00222.2015.

References

Yang Z, Wang X, Wang H, Hu L . Effects of TRPM8 on the proliferation and motility of prostate cancer PC-3 cells. Asian J Androl. 2009; 11(2):157-65. PMC: 3735032. DOI: 10.1038/aja.2009.1. View

Bautista D, Siemens J, Glazer J, Tsuruda P, Basbaum A, Stucky C . The menthol receptor TRPM8 is the principal detector of environmental cold. Nature. 2007; 448(7150):204-8. DOI: 10.1038/nature05910. View

Pawliczak R, Logun C, Madara P, Lawrence M, Woszczek G, Ptasinska A . Cytosolic phospholipase A2 Group IValpha but not secreted phospholipase A2 Group IIA, V, or X induces interleukin-8 and cyclooxygenase-2 gene and protein expression through peroxisome proliferator-activated receptors gamma 1 and 2 in human lung cells. J Biol Chem. 2004; 279(47):48550-61. DOI: 10.1074/jbc.M408926200. View

Smani T, Zakharov S, Csutora P, Leno E, Trepakova E, Bolotina V . A novel mechanism for the store-operated calcium influx pathway. Nat Cell Biol. 2004; 6(2):113-20. DOI: 10.1038/ncb1089. View

Bavencoffe A, Gkika D, Kondratskyi A, Beck B, Borowiec A, Bidaux G . The transient receptor potential channel TRPM8 is inhibited via the alpha 2A adrenoreceptor signaling pathway. J Biol Chem. 2010; 285(13):9410-9419. PMC: 2843190. DOI: 10.1074/jbc.M109.069377. View

Gkika D, Flourakis M, Lemonnier L, Prevarskaya N . PSA reduces prostate cancer cell motility by stimulating TRPM8 activity and plasma membrane expression. Oncogene. 2010; 29(32):4611-6. DOI: 10.1038/onc.2010.210. View

Lefkimmiatis K, Srikanthan M, Maiellaro I, Moyer M, Curci S, Hofer A . Store-operated cyclic AMP signalling mediated by STIM1. Nat Cell Biol. 2009; 11(4):433-42. DOI: 10.1038/ncb1850. View

Clapham D . TRP channels as cellular sensors. Nature. 2003; 426(6966):517-24. DOI: 10.1038/nature02196. View

Colburn R, Lubin M, Stone Jr D, Wang Y, Lawrence D, DAndrea M . Attenuated cold sensitivity in TRPM8 null mice. Neuron. 2007; 54(3):379-86. DOI: 10.1016/j.neuron.2007.04.017. View

10.

Rohacs T, Lopes C, Michailidis I, Logothetis D . PI(4,5)P2 regulates the activation and desensitization of TRPM8 channels through the TRP domain. Nat Neurosci. 2005; 8(5):626-34. DOI: 10.1038/nn1451. View

11.

Wondergem R, Ecay T, Mahieu F, Owsianik G, Nilius B . HGF/SF and menthol increase human glioblastoma cell calcium and migration. Biochem Biophys Res Commun. 2008; 372(1):210-5. DOI: 10.1016/j.bbrc.2008.05.032. View

12.

Brauchi S, Orio P, Latorre R . Clues to understanding cold sensation: thermodynamics and electrophysiological analysis of the cold receptor TRPM8. Proc Natl Acad Sci U S A. 2004; 101(43):15494-9. PMC: 523461. DOI: 10.1073/pnas.0406773101. View

13.

Andersson D, Nash M, Bevan S . Modulation of the cold-activated channel TRPM8 by lysophospholipids and polyunsaturated fatty acids. J Neurosci. 2007; 27(12):3347-55. PMC: 2726637. DOI: 10.1523/JNEUROSCI.4846-06.2007. View

14.

Gentry C, Stoakley N, Andersson D, Bevan S . The roles of iPLA2, TRPM8 and TRPA1 in chemically induced cold hypersensitivity. Mol Pain. 2010; 6:4. PMC: 2822744. DOI: 10.1186/1744-8069-6-4. View

15.

Bidaux G, Flourakis M, Thebault S, Zholos A, Beck B, Gkika D . Prostate cell differentiation status determines transient receptor potential melastatin member 8 channel subcellular localization and function. J Clin Invest. 2007; 117(6):1647-57. PMC: 1866249. DOI: 10.1172/JCI30168. View

16.

Xing H, Chen M, Ling J, Tan W, Gu J . TRPM8 mechanism of cold allodynia after chronic nerve injury. J Neurosci. 2007; 27(50):13680-90. PMC: 6673615. DOI: 10.1523/JNEUROSCI.2203-07.2007. View

17.

Vanden Abeele F, Zholos A, Bidaux G, Shuba Y, Thebault S, Beck B . Ca2+-independent phospholipase A2-dependent gating of TRPM8 by lysophospholipids. J Biol Chem. 2006; 281(52):40174-82. DOI: 10.1074/jbc.M605779200. View

18.

Sabnis A, Shadid M, Yost G, Reilly C . Human lung epithelial cells express a functional cold-sensing TRPM8 variant. Am J Respir Cell Mol Biol. 2008; 39(4):466-74. PMC: 2551706. DOI: 10.1165/rcmb.2007-0440OC. View

19.

Michel M, Vrydag W . Alpha1-, alpha2- and beta-adrenoceptors in the urinary bladder, urethra and prostate. Br J Pharmacol. 2006; 147 Suppl 2:S88-119. PMC: 1751487. DOI: 10.1038/sj.bjp.0706619. View

20.

Johnson C, Melanaphy D, Purse A, Stokesberry S, Dickson P, Zholos A . Transient receptor potential melastatin 8 channel involvement in the regulation of vascular tone. Am J Physiol Heart Circ Physiol. 2009; 296(6):H1868-77. PMC: 2716108. DOI: 10.1152/ajpheart.01112.2008. View