TRPV4 activates autonomic and behavioural warmth-defence responses in Wistar rats.
OBJECTIVE
In this study, we aimed at investigating the involvement of the warmth-sensitive channel - TRPV4 (in vitro sensitive to temperatures in the range of approx. 24-34 °C) - on the thermoregulatory mechanisms in rats.


METHODS
We treated rats with a chemical selective agonist (RN-1747) and two antagonists (RN-1734 and HC-067047) of the TRPV4 channel and measured core body temperature, metabolism, heat loss index and preferred ambient temperature.


RESULTS
Our data revealed that chemical activation of TRPV4 channels by topical application of RN-1747 on the skin leads to hypothermia and this effect was blocked by the pre-treatment with the selective antagonist of this channel. Intracerebroventricular treatment with RN-1747 did not cause hypothermia, indicating that the observed response was indeed due to activation of TRPV4 channels in the periphery. Intravenous blockade of this channel with HC-067047 caused an increase in core body temperature at ambient temperature of 26 and 30 °C, but not at 22 and 32 °C. At 26 °C, HC-067047-induced hyperthermia was accompanied by increase in oxygen consumption (an index of thermogenesis), while chemical stimulation of TRPV4 increased tail heat loss, indicating that these two autonomic thermoeffectors in the rat are modulated through TRPV4 channels. Furthermore, rats chemically stimulated with TRPV4 agonist choose colder ambient temperatures and cold-seeking behaviour after thermal stimulation (28-31 °C) was inhibited by TRPV4 antagonist.


CONCLUSIONS
Our results suggest, for the first time, that TRPV4 channel is involved in the recruitment of behavioural and autonomic warmth-defence responses to regulate core body temperature.
Graduate Program on Neuroscience and Cognition, Universidade Federal do ABC (UFABC), São Bernardo do Campo, SP, Brazil.
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Vizin
Department of Animal Morphology and Physiology, College of Agricultural and Veterinary Sciences, São Paulo State University, Jaboticabal, SP, Brazil.|Joint UFSCar-UNESP Graduate Program of Physiological Sciences, Sao Carlos, SP, Brazil.|National Institute of Science and Technology in Comparative Physiology (INCT - Fisiologia Comparada), Jaboticabal, SP, Brazil.
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Scarpellini
Graduate Program on Neuroscience and Cognition, Universidade Federal do ABC (UFABC), São Bernardo do Campo, SP, Brazil.
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Ishikawa
Department of Animal Morphology and Physiology, College of Agricultural and Veterinary Sciences, São Paulo State University, Jaboticabal, SP, Brazil.|National Institute of Science and Technology in Comparative Physiology (INCT - Fisiologia Comparada), Jaboticabal, SP, Brazil.
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Correa
Graduate Program on Neuroscience and Cognition, Universidade Federal do ABC (UFABC), São Bernardo do Campo, SP, Brazil.
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de Souza
Department of Animal Morphology and Physiology, College of Agricultural and Veterinary Sciences, São Paulo State University, Jaboticabal, SP, Brazil.|National Institute of Science and Technology in Comparative Physiology (INCT - Fisiologia Comparada), Jaboticabal, SP, Brazil.
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Gargaglioni
Graduate Program on Neuroscience and Cognition, Universidade Federal do ABC (UFABC), São Bernardo do Campo, SP, Brazil.|Natural and Humanities Science Center, Universidade Federal do ABC (UFABC), São Bernardo do Campo, SP, Brazil.
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Carrettiero
Department of Animal Morphology and Physiology, College of Agricultural and Veterinary Sciences, São Paulo State University, Jaboticabal, SP, Brazil.|National Institute of Science and Technology in Comparative Physiology (INCT - Fisiologia Comparada), Jaboticabal, SP, Brazil.
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Bícego
Graduate Program on Neuroscience and Cognition, Universidade Federal do ABC (UFABC), São Bernardo do Campo, SP, Brazil.|Natural and Humanities Science Center, Universidade Federal do ABC (UFABC), São Bernardo do Campo, SP, Brazil.
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Almeida
D000818:Animals; D001341:Autonomic Nervous System / Q000502:physiology*; D001522:Behavior, Animal / Q000502:physiology*; D001831:Body Temperature / Q000502:physiology*; D001833:Body Temperature Regulation / Q000502:physiology*; D003080:Cold Temperature; D007035:Hypothermia / Q000503:physiopathology; D008297:Male; D017208:Rats, Wistar; D050916:TRPV Cation Channels / Q000378:metabolism*; D022722:Thermogenesis / Q000502:physiology*
D050916:TRPV Cation Channels; C486577:Trpv4 protein, rat
TRPV4 manipulation; tail vasomotor tone; thermogenesis; thermopreferendum; thermoregulation; warmth sensor