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TRPA1

  • Peter M. Zygmunt
  • Edward D. Högestätt
Chapter
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 222)

Abstract

The transient receptor potential ankyrin subtype 1 protein (TRPA1) is a nonselective cation channel permeable to Ca2+, Na+, and K+. TRPA1 is a promiscuous chemical nocisensor that is also involved in noxious cold and mechanical sensation. It is present in a subpopulation of Aδ- and C-fiber nociceptive sensory neurons as well as in other sensory cells including epithelial cells. In primary sensory neurons, Ca2+ and Na+ flowing through TRPA1 into the cell cause membrane depolarization, action potential discharge, and neurotransmitter release both at peripheral and central neural projections. In addition to being activated by cysteine and lysine reactive electrophiles and oxidants, TRPA1 is indirectly activated by pro-inflammatory agents via the phospholipase C signaling pathway, in which cytosolic Ca2+ is an important regulator of channel gating. The finding that non-electrophilic compounds, including menthol and cannabinoids, activate TRPA1 may provide templates for the design of non-tissue damaging activators to fine-tune the activity of TRPA1 and raises the possibility that endogenous ligands sharing binding sites with such non-electrophiles exist and regulate TRPA1 channel activity. TRPA1 is promising as a drug target for novel treatments of pain, itch, and sensory hyperreactivity in visceral organs including the airways, bladder, and gastrointestinal tract.

Keywords

Nociceptor Sensory transduction Pain Hydrogen sulfide Hyperalgesia Chemosensitivity Mechanotransduction Thermosensitive Irritants Allyl isothiocyanate Menthol Cannabinoid Mustard oil TRPA1 TRPV1 

Notes

Acknowledgment

We would like to thank Swedish Research Council (2010-3347 and 2010-5787) and Lund University for their fundings.

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© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Clinical and Experimental Pharmacology, Clinical Chemistry, Department of Laboratory MedicineLund University, Skåne University HospitalLundSweden

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