title: Systemic Administration of the TRPV3 Ion Channel Agonist Carvacrol Induces Hypothermia in Conscious Rodents.
abstract: Therapeutic hypothermia is a promising new strategy for neuroprotection. However, the methods for safe and effective hypothermia induction in conscious patients are lacking. The current study explored the Transient Receptor Potential Vanilloid 3 (TRPV3) channel activation by the agonist carvacrol as a potential hypothermic strategy. It was found that carvacrol lowers core temperature after intraperitoneal and intravenous administration in mice and rats. However, the hypothermic effect at safe doses was modest, while higher intravenous doses of carvacrol induced a pronounced drop in blood pressure and substantial toxicity. Experiments on the mechanism of the hypothermic effect in mice revealed that it was associated with a decrease in whole-body heat generation, but not with a change in cold-seeking behaviors. In addition, the hypothermic effect was lost at cold ambient temperature. Our findings suggest that although TRPV3 agonism induces hypothermia in rodents, it may have a limited potential as a novel pharmacological method for induction of hypothermia in conscious patients due to suboptimal effectiveness and high toxicity.
authors.affiliation: Department of Molecular Physiology and Biophysics Graduate Program, Cardiovascular Sciences Track, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Viktor V
authors.initials: VV
authors.lastname: Feketa
authors.affiliation: Department of Molecular Physiology and Biophysics Graduate Program, Cardiovascular Sciences Track, Baylor College of Medicine, Houston, Texas, United States of America; Department of Anesthesiology, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Sean P
authors.initials: SP
authors.lastname: Marrelli
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D001833:Body Temperature Regulation / Q000187:drug effects* / Q000502:physiology; D000081007:Cymenes; D004305:Dose-Response Relationship, Drug; D007036:Hypothermia, Induced; D008297:Male; D051379:Mice; D039821:Monoterpenes / Q000009:adverse effects / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050916:TRPV Cation Channels / Q000819:agonists* / Q000378:metabolism
chemical_list: D000081007:Cymenes; D039821:Monoterpenes; D050916:TRPV Cation Channels; C505767:TRPV3 protein, rat; C486760:Trpv3 protein, mouse; C073316:carvacrol