ArticleThe Journal of biological chemistry2013
Carboxyl-terminal domain of transient receptor potential vanilloid 1 contains distinct segments differentially involved in capsaicin- and heat-induced desensitization.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 46 citations in OpenAlex.
- Inactivation Switch for Run-up in TRPV2.Research square · 2026Article
- Automated thermal gradient test for unprovoked assessment of nociceptive preference in rodents.Frontiers in behavioral neuroscience · 2025Article
- Temperature-Dependent Activation of Thermosensitive Transient Receptor Potential Channels.Advances in experimental medicine and biology · 2024Review
- Analyzing the Antinociceptive Effect of Interleukin-31 in Mice.International journal of molecular sciences · 2023Article
- A molecular perspective on identifying TRPV1 thermosensitive regions and disentangling polymodal activation.Temperature (Austin, Tex.) · 2023Review
- Targeting TRP channels: recent advances in structure, ligand binding, and molecular mechanisms.Frontiers in molecular neuroscience · 2023Review
- Shaoyao Gancao Decoction Ameliorates Paclitaxel-Induced Peripheral Neuropathy via Suppressing TRPV1 and TLR4 Signaling Expression in Rats.Drug design, development and therapy · 2022Article
- Mapping temperature-dependent conformational change in the voltage-sensing domain of an engineered heat-activated KProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Fight fire with fire: Neurobiology of capsaicin-induced analgesia for chronic pain.Pharmacology & therapeutics · 2021Review
- Structural basis for promiscuous action of monoterpenes on TRP channels.Communications biology · 2021Article
- Review
- TRP Channels, Conformational Flexibility, and the Lipid Membrane.The Journal of membrane biology · 2020Review
- Molecular basis for heat desensitization of TRPV1 ion channels.Nature communications · 2019Article
- Article
- Cannabinoid Hyperemesis.Medical cannabis and cannabinoids · 2019Review
- Heat activation is intrinsic to the pore domain of TRPV1.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Use of Capsaicin to Treat Pain: Mechanistic and Therapeutic Considerations.Pharmaceuticals (Basel, Switzerland) · 2016Review
- Article
- Evolution of Heat Sensors Drove Shifts in Thermosensation between Xenopus Species Adapted to Different Thermal Niches.The Journal of biological chemistry · 2016Article
- Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Multiple Ca(2+)-dependent processes are involved in capsaicin-induced desensitization of transient receptor potential vanilloid 1 (TRPV1), but desensitization of TRPV1 by heat occurs even in the absence of extracellular Ca(2+), although the mechanisms are unknown. In this study, we tested the hypothesis that capsaicin and heat desensitize TRPV1 through distinct mechanisms involving distinct structural segments of TRPV1. In HEK293 cells that heterologously express TRPV1, we found that heat-induced desensitization was not affected by the inclusion of intracellular ATP or alanine mutation of Lys(155), both of which attenuate capsaicin-induced desensitization, suggesting that heat-induced desensitization occurs through mechanisms distinct from capsaicin-induced desensitization. To determine protein domains involved in heat-induced desensitization, we generated chimeric proteins between TRPV1 and TRPV3, a heat-gated channel lacking heat-induced desensitization. We found that TRPV1 with the carboxyl-terminal domain (CTD) of TRPV3 retained heat activation but was impaired in heat-induced desensitization. Further experiments using chimeric or deletion mutants within TRPV1 CTD indicated that the distal half of CTD regulates the activation and desensitization of TRPV1 in modality-specific manners. Within the distal CTD, we identified two segments that distinctly regulated capsaicin- and heat-induced desensitization. The results suggest that the activation and desensitization of TRPV1 by capsaicin and heat can be modulated differentially and disproportionally through different regions of TRPV1 CTD. Identifying the domains involved in thermal regulation of TRPV1 may facilitate the development of novel anti-hyperalgesic approaches aimed at attenuating activation and enhancing desensitization of TRPV1 by thermal stimuli.
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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.