RGD Reference Report - The transient receptor potential channel TRPM8 is inhibited via the alpha 2A adrenoreceptor signaling pathway. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

The transient receptor potential channel TRPM8 is inhibited via the alpha 2A adrenoreceptor signaling pathway.

Authors: Bavencoffe, A  Gkika, D  Kondratskyi, A  Beck, B  Borowiec, AS  Bidaux, G  Busserolles, J  Eschalier, A  Shuba, Y  Skryma, R  Prevarskaya, N 
Citation: Bavencoffe A, etal., J Biol Chem. 2010 Mar 26;285(13):9410-9. Epub 2010 Jan 28.
RGD ID: 6480493
Pubmed: PMID:20110357   (View Abstract at PubMed)
PMCID: PMC2843190   (View Article at PubMed Central)
DOI: DOI:10.1074/jbc.M109.069377   (Journal Full-text)

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.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Adra2aRatthermoception  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Adra2a  (adrenoceptor alpha 2A)


Additional Information