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Structural determinant of TRPV1 desensitization interacts with calmodulin
Open accessAbstract
The capsaicin receptor, TRPV1 (VR1), is a sensory neuron-specific ion channel that serves as a polymodal detector of pain-producing chemical and physical stimuli. Extracellular Ca 2+ -dependent desensitization of TRPV1 observed in patch–clamp experiments when using both heterologous expression systems and native sensory ganglia is thought to be one mechanism underlying the paradoxical effectiveness of capsaicin as an analgesic therapy. Here, we show that the Ca 2+ -binding protein calmodulin binds to a 35-aa segment in the C terminus of TRPV1, and that disruption of the calmodulin-binding segment prevents TRPV1 desensitization. Compounds that interfere with the 35-aa segment could therefore prove useful in the treatment of pain.
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Cites
Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide
Zygmunt, P. M., Petersson, J., Andersson, D. A., Chuang, H.-H., Sørgård, M., Di Marzo, V., Julius, D., & Högestätt, E. D. (1999) · Nature · doi:10.1038/22761 · Cited by 2,142
Cited by
Regulation of the Ca2+ Sensitivity of the Nonselective Cation Channel TRPM4
Nilius, B., Prenen, J., Tang, J., Wang, C., Owsianik, G., Janssens, A., Voets, T., & Zhu, M. X. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m411089200 · Cited by 301
Garami, A., Shimansky, Y. P., Rumbus, Z., Vizin, R. C. L., Farkas, N., Hegyi, J., Szakacs, Z., Solymar, M., Csenkey, A., Chiche, D. A., et al. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107474 · Cited by 159
TRPV1 and Endocannabinoids: Emerging Molecular Signals that Modulate Mammalian Vision
Ryskamp, D., Redmon, S., Jo, A., & Križaj, D. (2014) · Cells · doi:10.3390/cells3030914 · Cited by 60
Metadata
- Authors
- Numazaki, M., Tominaga, T., Takeuchi, K., Murayama, N., Toyooka, H., & Tominaga, M.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2003-06-13
- Volume
- 100
- Issue
- 13
- Pages
- 8002-8006
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2134824442
- Cited by
- 366
- References
- 1
- FWCI
- 9.23
- Type
- journal article
- Language
- en
- Open access
- green
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- Numazaki, M., Tominaga, T., Takeuchi, K., Murayama, N., Toyooka, H., & Tominaga, M. (2003). Structural determinant of TRPV1 desensitization interacts with calmodulin. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1337252100
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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