ArticleThe Journal of biological chemistry2011
Complex regulation of the TRPM8 cold receptor channel: role of arachidonic acid release following M3 muscarinic receptor stimulation.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 23 citations in OpenAlex.
- EMC3 is critical for CFTR function and calcium mobilization in the mouse intestinal epithelium.American journal of physiology. Gastrointestinal and liver physiology · 2025Article
- Bidirectional TRP/L Type CaBiomolecules · 2023Article
- Comprehensive Pan-Cancer Analysis of TRPM8 in Tumor Metabolism and Immune Escape.Frontiers in oncology · 2022Article
- Actions and Mechanisms of Polyunsaturated Fatty Acids on Voltage-Gated Ion Channels.Frontiers in physiology · 2017Review
- Ion channel mechanisms of rat tail artery contraction-relaxation by menthol involving, respectively, TRPM8 activation and L-type Ca2+ channel inhibition.American journal of physiology. Heart and circulatory physiology · 2016Article
- ThermoTRPs and Pain.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2016Review
- TRP channel-associated factors are a novel protein family that regulates TRPM8 trafficking and activity.The Journal of cell biology · 2015Article
- Trafficking of ThermoTRP Channels.Membranes · 2014Review
- Sensory TRP channel interactions with endogenous lipids and their biological outcomes.Molecules (Basel, Switzerland) · 2014Review
- Down-regulation of TRPM8 in pulmonary arteries of pulmonary hypertensive rats.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2013Article
- From urgency to frequency: facts and controversies of TRPs in the lower urinary tract.Nature reviews. Urology · 2011Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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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.