Supercooling Agent Icilin Blocks a Warmth-Sensing Ion Channel TRPV3

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 a...

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Main Authors: Muhammad Azhar Sherkheli, Guenter Gisselmann, Hanns Hatt
Format: Article
Language:English
Published: Wiley 2012-01-01
Series:The Scientific World Journal
Online Access:http://dx.doi.org/10.1100/2012/982725
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author Muhammad Azhar Sherkheli
Guenter Gisselmann
Hanns Hatt
author_facet Muhammad Azhar Sherkheli
Guenter Gisselmann
Hanns Hatt
author_sort Muhammad Azhar Sherkheli
collection DOAJ
description 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.
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spelling doaj-art-50fb53a922024967ae3387a003efad612025-08-20T02:05:10ZengWileyThe Scientific World Journal1537-744X2012-01-01201210.1100/2012/982725982725Supercooling Agent Icilin Blocks a Warmth-Sensing Ion Channel TRPV3Muhammad Azhar Sherkheli0Guenter Gisselmann1Hanns Hatt2Department of Cell Physiology, Ruhr University Bochum, 44801 Bochum, GermanyDepartment of Cell Physiology, Ruhr University Bochum, 44801 Bochum, GermanyDepartment of Cell Physiology, Ruhr University Bochum, 44801 Bochum, GermanyTransient 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.http://dx.doi.org/10.1100/2012/982725
spellingShingle Muhammad Azhar Sherkheli
Guenter Gisselmann
Hanns Hatt
Supercooling Agent Icilin Blocks a Warmth-Sensing Ion Channel TRPV3
The Scientific World Journal
title Supercooling Agent Icilin Blocks a Warmth-Sensing Ion Channel TRPV3
title_full Supercooling Agent Icilin Blocks a Warmth-Sensing Ion Channel TRPV3
title_fullStr Supercooling Agent Icilin Blocks a Warmth-Sensing Ion Channel TRPV3
title_full_unstemmed Supercooling Agent Icilin Blocks a Warmth-Sensing Ion Channel TRPV3
title_short Supercooling Agent Icilin Blocks a Warmth-Sensing Ion Channel TRPV3
title_sort supercooling agent icilin blocks a warmth sensing ion channel trpv3
url http://dx.doi.org/10.1100/2012/982725
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