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Complex Regulation of TRPV1 and Related Thermo-TRPs: Implications for Therapeutic Intervention

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Transient Receptor Potential Channels

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 704))

Abstract

The capsaicin receptor TRPV1 (Transient Receptor Potential, Vanilloid family member 1), the founding member of the heat-sensitive TRP (“thermo-TRP”) channel family, plays a pivotal role in pain transduction. There is mounting evidence that TRPV1 regulation is complex and is manifest at many levels, from gene expression through post-translational modification and formation of receptor heteromers to subcellular compartmentalization and association with regulatory proteins. These mechanisms are believed to be involved both in disease-related changes in TRPV1 expression, and the long-lasting refractory state, referred to as “desensitization”, that follows TRPV1 agonist treatment. The signaling cascades that regulate TRPV1 and related thermo-TRP channels are only beginning to be understood. Here we review our current knowledge in this rapidly changing field. We propose that the complex regulation of TRPV1 may be exploited for therapeutic purposes, with the ultimate goal being the development of novel, innovative agents that target TRPV1 in diseased, but not healthy, tissues. Such compounds are expected to be devoid of the side-effects (e.g. hyperthermia and impaired noxious heat sensation) that plague the clinical use of existing TRPV1 antagonists.

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Acknowledgments

This work was supported by grants from el Ministerio de Ciencia e Innovación (MICINN) (BFU2009-08346 to A.F.-M. and SAF2007-63193 to R.P.-C.); the Consolider-Ingenio 2010 (MICINN, CSD2008-00005 to A.F.-M and R.P.-C.), la Fundació La Marató de TV3 (to A.F.-M and R.P.-C.).

Support for Dr. Qin was by NIH GM65994. We thank Dr. Azucena Perez Burgos for creating Figures 1, 2 and 3.

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Authors and Affiliations

  1. Centro de Investigación Príncipe Felipe, Valencia, Spain

    Rosa Planells-Cases

  2. Instituto de Biología Molecular y Celular, Universidad Miguel Hernández, Elche, Spain

    Pierluigi Valente & Antonio Ferrer-Montiel

  3. Department of Neuroscience and Brain Technologies, Italian Institute of Technology – IIT, Genova, Italy

    Pierluigi Valente

  4. Department of Physiology and Biophysical Sciences, State University of New York at Buffalo, Buffalo, NY, USA

    Feng Qin

  5. Department of Pathology, Monmouth Medical Center, Long Branch, NJ, 07740, USA

    Arpad Szallasi

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  1. Rosa Planells-Cases
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  2. Pierluigi Valente
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  3. Antonio Ferrer-Montiel
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  4. Feng Qin
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  5. Arpad Szallasi
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Correspondence to Arpad Szallasi .

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  1. Dept. Clinical Research & Education, Södersjukhuset, Karolinska Institutet, Stockholm, 118 83, Sweden

    Md. Shahidul Islam

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Planells-Cases, R., Valente, P., Ferrer-Montiel, A., Qin, F., Szallasi, A. (2011). Complex Regulation of TRPV1 and Related Thermo-TRPs: Implications for Therapeutic Intervention. In: Islam, M. (eds) Transient Receptor Potential Channels. Advances in Experimental Medicine and Biology, vol 704. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-0265-3_27

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