The Transient Receptor Potential Channel TRPM8 Is Inhibited via the α2A Adrenoreceptor Signaling Pathway
| Autor: | Dimitra Gkika, Alain Eschalier, Artem Kondratskyi, Roman Skryma, Anne Sophie Borowiec, Benjamin Beck, Yaroslav M. Shuba, Gabriel Bidaux, Jérôme Busserolles, Natalia Prevarskaya, Alexis Bavencoffe |
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| Přispěvatelé: | Rôle des canaux ioniques membranaires et du calcium intracellulaire dans la physiopathologie de la prostate, Université de Lille, Sciences et Technologies-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Physiologie Cellulaire : Canaux ioniques, inflammation et cancer - U 1003 (PHYCELL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine (NASU), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pharmacologie fondamentale et clinique de la douleur, Neuro-Dol (Neuro-Dol), Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Santé et de la Recherche Médicale (INSERM), bidaux, gabriel, Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA) |
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Patch-Clamp Techniques
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology Gi alpha subunit TRPM Cation Channels Stimulation Biology Receptors Adrenergic alpha-2 -- metabolism Biochemistry Models Biological Cell Line Receptors G-Protein-Coupled 03 medical and health sciences Transient receptor potential channel 0302 clinical medicine Ganglia Spinal -- metabolism Receptors Adrenergic alpha-2 Ganglia Spinal TRPM8 [SDV.BBM] Life Sciences [q-bio]/Biochemistry Molecular Biology TRPM Cation Channels -- metabolism Animals Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Neurons -- metabolism Phosphorylation Rats Wistar Protein kinase A Receptor Molecular Biology 030304 developmental biology Neurons 0303 health sciences Cyclic AMP-Dependent Protein Kinases -- metabolism Temperature [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology Cell Biology Receptors G-Protein-Coupled -- metabolism Sciences bio-médicales et agricoles Cyclic AMP-Dependent Protein Kinases 3. Good health Cell biology Rats Mutagenesis Signal transduction 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Journal of Biological Chemistry Journal of Biological Chemistry, 2010, 285 (13), pp.9410-9419. ⟨10.1074/jbc.M109.069377⟩ The Journal of biological chemistry, 285 (13 Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2010, 285 (13), pp.9410-9419. ⟨10.1074/jbc.M109.069377⟩ |
| ISSN: | 0021-9258 1083-351X |
| DOI: | 10.1074/jbc.M109.069377⟩ |
| Popis: | 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. Journal Article Research Support, Non-U.S. Gov't info:eu-repo/semantics/published |
| Databáze: | OpenAIRE |
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