Transient receptor potential melastatin 8 (TRPM8) channels are involved in body temperature regulation
| Autor: | Sonya G. Lehto, Dawn Zhu, Narender R. Gavva, Carl Davis, Sara Rao, Weiya Wang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Male
medicine.medical_specialty TRPM Cation Channels CHO Cells Pharmacology Rats Sprague-Dawley Cellular and Molecular Neuroscience Transient receptor potential channel chemistry.chemical_compound Inhibitory Concentration 50 Mice Body temperature regulation In vivo Compound 496 Internal medicine Cricetinae Membrane Transport Modulators TRPM8 medicine lcsh:Pathology Animals Naphthyridines AMG8788 AMG9678 Dose-Response Relationship Drug Research Antagonist Icilin Thermoregulation Rats Mice Inbred C57BL Dose–response relationship AMG0635 Anesthesiology and Pain Medicine Endocrinology TRPM8 antagonist chemistry Molecular Medicine Menthol Ion Channel Gating AMG2850 lcsh:RB1-214 |
| Zdroj: | Molecular Pain, Vol 8, Iss 1, p 36 (2012) Molecular Pain |
| ISSN: | 1744-8069 |
| Popis: | Background: Transient receptor potential cation channel subfamily M member 8 (TRPM8) is activated by cold temperature in vitro and has been demonstrated to act as a ‘cold temperature sensor’ in vivo. Although it is known that agonists of this ‘cold temperature sensor’, such as menthol and icilin, cause a transient increase in body temperature (Tb), it is not known if TRPM8 plays a role in Tb regulation. Since TRPM8 has been considered as a potential target for chronic pain therapeutics, we have investigated the role of TRPM8 in Tb regulation. Results: We characterized five chemically distinct compounds (AMG0635, AMG2850, AMG8788, AMG9678, and Compound 496) as potent and selective antagonists of TRPM8 and tested their effects on Tb in rats and mice implanted with radiotelemetry probes. All five antagonists used in the study caused a transient decrease in Tb (maximum decrease of 0.98°C). Since thermoregulation is a homeostatic process that maintains Tb about 37°C, we further evaluated whether repeated administration of an antagonist attenuated the decrease in Tb. Indeed, repeated daily administration of AMG9678 for four consecutive days showed a reduction in the magnitude of the Tb decrease Day 2 onwards. Conclusions: The data reported here demonstrate that TRPM8 channels play a role in Tb regulation. Further, a reduction of magnitude in Tb decrease after repeated dosing of an antagonist suggests that TRPM8's role in Tb maintenance may not pose an issue for developing TRPM8 antagonists as therapeutics. |
| Databáze: | OpenAIRE |
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