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Updated: Jun 16, 2026

A Simple and Inexpensive Method for Determining Cold Sensitivity and Adaptation in Mice
Published on: March 17, 2015
The transient receptor potential channel TRPM8 is inhibited via the alpha 2A adrenoreceptor signaling pathway
Alexis Bavencoffe1, Dimitra Gkika1, Artem Kondratskyi2
1INSERM U800, Equipe Labellisée par la Ligue Nationale contre le Cancer, Université des Sciences et Technologies de Lille (USTL), F59655 Villeneuve d'Ascq, France.
Abstract:
The transient receptor potential channel melastatin member 8 (TRPM8) is expressed in sensory neurons, where it constitutes the main receptor of environmental innocuous cold (10-25 degrees C). Among several types of G protein-coupled receptors expressed in sensory neurons, G(i)-coupled alpha 2A-adrenoreceptor (alpha 2A-AR), is known to be involved in thermoregulation; however, the underlying molecular mechanisms remain poorly understood. Here we demonstrated that stimulation of alpha 2A-AR inhibited TRPM8 in sensory neurons from rat dorsal root ganglia (DRG). In addition, using specific pharmacological and molecular tools combined with patch-clamp current recordings, we found that in heterologously expressed HEK-293 (human embryonic kidney) cells, TRPM8 channel is inhibited by the G(i) protein/adenylate cyclase (AC)/cAMP/protein kinase A (PKA) signaling cascade. We further identified the TRPM8 S9 and T17 as two key PKA phosphorylation sites regulating TRPM8 channel activity. We therefore propose that inhibition of TRPM8 through the alpha 2A-AR signaling cascade could constitute a new mechanism of modulation of thermosensation in both physiological and pathological conditions.
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