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The Scientific World Journal
Volume 2012, Article ID 982725, 8 pages
http://dx.doi.org/10.1100/2012/982725
Research Article

Supercooling Agent Icilin Blocks a Warmth-Sensing Ion Channel TRPV3

1Department of Cell Physiology, Ruhr University Bochum, 44801 Bochum, Germany
2Department of Pharmaceutical Sciences, Faculty of Pharmacy, Superior University, Raiwind Road, Lahore 54660, Pakistan

Received 30 October 2011; Accepted 30 November 2011

Academic Editors: R. Inoue and J.-B. Peng

Copyright © 2012 Muhammad Azhar Sherkheli et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Transient receptor potential vanilloid subtype 3 (TRPV3) is a thermosensitive ion channel expressed in a variety of neural cells and in keratinocytes. It is activated by warmth (33–39°C), and its responsiveness is dramatically increased at nociceptive temperatures greater than 40°C. Monoterpenoids and 2-APB are chemical activators of TRPV3 channels. We found that Icilin, a known cooling substance and putative ligand of TRPM8, reversibly inhibits TRPV3 activity at nanomolar concentrations in expression systems like Xenopus laeves oocytes, HEK-293 cells, and in cultured human keratinocytes. Our data show that icilin's antagonistic effects for the warm-sensitive TRPV3 ion channel occurs at very low concentrations. Therefore, the cooling effect evoked by icilin may at least in part be due to TRPV3 inhibition in addition to TRPM8 potentiation. Blockade of TRPV3 activity by icilin at such low concentrations might have important implications for overall cooling sensations detected by keratinocytes and free nerve endings in skin. We hypothesize that blockage of TRPV3 might be a signal for cool-sensing systems (like TRPM8) to beat up the basal activity resulting in increased cold perception when warmth sensors (like TRPV3) are shut off.