ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2005
Downregulation of transient receptor potential melastatin 8 by protein kinase C-mediated dephosphorylation.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
84 citing papers in PubMed, 161 citations in OpenAlex.
- Menthol-induced activation of TRPM8 receptors increases cutaneous blood flow across the dermatome.Microvascular research · 2022Trial
- Study on the discovery of lung-descending herbs and bioactive constituents using TRP channel-functionalized screening.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Activation of central and peripheral transient receptor potential melastatin 8 increases susceptibility to spreading depolarization and facilitates trigeminal neuroinflammation.The journal of headache and pain · 2025Article
- Ion channels of cold transduction and transmission.The Journal of general physiology · 2024Review
- Interaction of Calmodulin with TRPM: An Initiator of Channel Modulation.International journal of molecular sciences · 2023Review
- PKC regulation of ion channels: The involvement of PIPThe Journal of biological chemistry · 2022Review
- Bradykinin-Induced Sensitization of Transient Receptor Potential Channel Melastatin 3 Calcium Responses in Mouse Nociceptive Neurons.Frontiers in cellular neuroscience · 2022Article
- Mechanistic investigations of diabetic ocular surface diseases.Frontiers in endocrinology · 2022Review
- Cold stimuli, hot topic: An updated review on the biological activity of menthol in relation to inflammation.Frontiers in immunology · 2022Review
- The distinctive role of menthol in pain and analgesia: Mechanisms, practices, and advances.Frontiers in molecular neuroscience · 2022Review
- Constitutive Phosphorylation as a Key Regulator of TRPM8 Channel Function.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Oxaliplatin Causes Transient Changes in TRPM8 Channel Activity.International journal of molecular sciences · 2021Article
- Regulation of the cold-sensing TRPM8 channels by phosphoinositides and GChannels (Austin, Tex.) · 2020Review
- The cool things to know about TRPM8!Channels (Austin, Tex.) · 2020Review
- Negative Modulation of TRPM8 Channel Function by Protein Kinase C in Trigeminal Cold Thermoreceptor Neurons.International journal of molecular sciences · 2020Article
- Chronic morphine regulates TRPM8 channels via MOR-PKCβ signaling.Molecular brain · 2020Article
- Article
- Spinal and afferent PKC signaling mechanisms that mediate chronic pain in sickle cell disease.Neuroscience letters · 2019Review
- Direct GαCell reports · 2019Article
- Dry eye sensitizes cool cells to capsaicin-induced changes in activity via TRPV1.Journal of neurophysiology · 2019Article
24 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Transient receptor potential melastatin 8 (TRPM8) and transient receptor potential vanilloid 1 (TRPV1) are ion channels that detect cold and hot sensations, respectively. Their activation depolarizes the peripheral nerve terminals resulting in action potentials that propagate to brain via the spinal cord. These receptors also play a significant role in synaptic transmission between dorsal root ganglion (DRG) and dorsal horn (DH) neurons. Here, we show that TRPM8 is functionally downregulated by activation of protein kinase C (PKC) resulting in inhibition of membrane currents and increases in intracellular Ca2+ compared with upregulation of TRPV1 in cloned and native receptors. Bradykinin significantly downregulates TRPM8 via activation of PKC in DRG neurons. Activation of TRPM8 or TRPV1 at first sensory synapse between DRG and DH neurons leads to a robust increase in frequency of spontaneous/miniature EPSCs. PKC activation blunts TRPM8- and facilitates TRPV1-mediated synaptic transmission. Significantly, downregulation is attributable to PKC-mediated dephosphorylation of TRPM8 that could be reversed by phosphatase inhibitors. These findings suggest that inflammatory thermal hyperalgesia mediated by TRPV1 may be further aggravated by downregulation of TRPM8, because the latter could mediate the much needed cool/soothing sensation.
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What OpenQuestion holds
Registered trials
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.