R C L Vizin1, C da S Scarpellini2,3,4, D T Ishikawa1, G M Correa2,4, C O de Souza1, L H Gargaglioni2,4, D C Carrettiero1,5, K C Bícego2,4, M C Almeida1,5. 1. Graduate Program on Neuroscience and Cognition, Universidade Federal do ABC (UFABC), São Bernardo do Campo, SP, Brazil. 2. Department of Animal Morphology and Physiology, College of Agricultural and Veterinary Sciences, São Paulo State University, Jaboticabal, SP, Brazil. 3. Joint UFSCar-UNESP Graduate Program of Physiological Sciences, Sao Carlos, SP, Brazil. 4. National Institute of Science and Technology in Comparative Physiology (INCT - Fisiologia Comparada), Jaboticabal, SP, Brazil. 5. Natural and Humanities Science Center, Universidade Federal do ABC (UFABC), São Bernardo do Campo, SP, Brazil.
Abstract
AIM: 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. CONCLUSION: 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.
AIM: 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. CONCLUSION: 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.
Authors: John N Barrett; Samantha Rincon; Jayanti Singh; Cristina Matthewman; Julio Pasos; Ellen F Barrett; Suhrud M Rajguru Journal: J Neurophysiol Date: 2018-04-18 Impact factor: 2.714
Authors: Débora T Ishikawa; Robson Cristiano Lillo Vizin; Cristiane Oliveira de Souza; Daniel Carneiro Carrettiero; Andrej A Romanovsky; Maria Camila Almeida Journal: Pharmaceuticals (Basel) Date: 2019-02-02
Authors: Caroline Cristina-Silva; Lara Amaral-Silva; Kassia Moreira Santos; Gabriela Monteiro Correa; Welex Candido da Silva; Marcia H M R Fernandes; Glauber S F da Silva; Luciane H Gargaglioni; Maria C Almeida; Kenia C Bicego Journal: Front Physiol Date: 2022-07-15 Impact factor: 4.755