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Role of TRPV4 channels in thermoregulation in endotherms

Abstract

The thermo-TRPV4 channels are expressed in various tissues, including peripheral sensors in birds and peripheral and central sites in mammals. In rats, we have demonstrated that peripheral TRPV4 (possibly skin) appear active in a range of ambient temperature (Ta) higher than 22 ° C and lower than 32 ° C, being involved in activation of heat loss responses, both autonomic (tail vasodilation and inhibition of thermogenesis) and behavioral (selection of lower Tas). In these animals, in addition to the location on skin, TRPV4 are also expressed in the medial preoptic area (MPO), an important region involved in regulation of body temperature (Tc). There is evidence of increased expression of TRPV4 in MPO induced by systemic inflammation with endotoxin (LPS). From pilot experiments, showing an increase of Tc after TRPV4 antagonist intra-MPO injection, our hypothesis is that such channels act in the MPO as modulators of the activity of both autonomic and behavioral thermoeffectors during systemic inflammation. Testing this hypothesis is the first objective of the present study and, therefore, the following protocols will be performed: 1.1) - effect of the microinjection of HC-067047, selective antagonist of TRPV4 channels, in MPO on Tc, oxygen consumption (index of thermogenesis) and heat loss index (HLI) in control and LPS-treated rats in Ta below the activation range of peripheral TRPV4 (~ 21oC); 1.2) - effect of the microinjection of HC-067047 in the MPO on Tc, oxygen consumption and the HLI in control and LPS-treated rats in Ta within the activation range of peripheral TRPV4 (~ 28oC); and 1.3) - effect of the microinjection of HC-067047 in the MPO on Tc and preferred Ta of control and LPS-treated rats. Regarding birds, the picture is much less clear than in mammals. Despite the recognized presence of the TRPV4 in epithelial sensors in birds, the thermosensorial role of TRPV4 in these animals is still a matter for investigation. In this sense, using chickens as a model of precocious birds, the second aim of this study is to investigate whether the peripheral TRPV4 act as thermosensors and modulate autonomic and behavioral effectors in these animals. To this end, we will use 5 days old (Ta comfort ~ 32oC) and 3 weeks old (Ta comfort ~ 28oC) chicks to perform the following protocols: 2.1) - effect of chemical stimulation of peripheral TRPV4 with the agonist RN1747 on Tc, oxygen consumption and pulmonary ventilation (index of evaporative heat loss in birds) in 5-day old chicks in thermal comfort (Ta= 32 ° C); 2.2) - the effect of peripheral injection of antagonist HC067047 on Tc, oxygen consumption and ventilation in chicks in different Tas (26, 28, 30 and 32 ° C); 2.3) - the effect of antagonist and agonist injections on huddling behavior in 5-day old chicks; 2.4) - the effect of peripheral injection of antagonist HC067047 on Tc, oxygen consumption and ventilation of 3 weeks old chicks in different Tas (24, 26, 28 and 30 ° C); 2.5) - effect of inhibition of peripheral TRPV4 on the preferred Ta in thermal gradient after exposure to heat stimulus in 3 weeks old chicks; 2.6) - effect of chemical stimulation of peripheral TRPV4 on the preferred Ta in thermal gradient of 3 weeks old chicks. (AU)

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Scientific publications (8)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ZENA, LUCAS A.; DILLON, DANIELLE; HUNT, KATHLEEN E.; NAVAS, CARLOS A.; BICEGO, KENIA C.; BUCK, C. LOREN. Seasonal changes in plasma concentrations of the thyroid, glucocorticoid and reproductive hormones in the tegu lizard Salvator merianae. General and Comparative Endocrinology, v. 273, n. SI, p. 134-143, . (15/04849-6, 17/01652-2, 14/16320-7)
ZENA, LUCAS A.; DILLON, DANIELLE; HUNT, KATHLEEN E.; NAVAS, CARLOS A.; BUCK, C. LOREN; BICEGO, KENIA C.. Hormonal correlates of the annual cycle of activity and body temperature in the South-American tegu lizard (Salvator merianae). General and Comparative Endocrinology, v. 285, . (15/04849-6, 18/06192-2, 14/16320-7, 17/01652-2)
PATRONE, LUIS GUSTAVO A.; CAPALBO, ARETUZA C.; MARQUES, DANUZIA A.; BICEGO, KENIA C.; GARGAGLIONI, LUCIANE H.. An age- and sex-dependent role of catecholaminergic neurons in the control of breathing and hypoxic chemoreflex during postnatal development. Brain Research, v. 1726, . (15/04849-6, 16/24577-3)
RIPAMONTE, GABRIEL C.; GARGAGLIONI, LUCIANE H.. Functional role for preoptic CB1 receptors in breathing and thermal control. Neuroscience Letters, v. 732, . (15/04849-6, 19/09469-8)
SCARPELLINI, CAROLINA DA SILVEIRA; CRISTINA-SILVA, CAROLINE; BIANCARDI, VIVIAN; GARGAGLIONI, LUCIANE H.; ALMEIDA, MARIA CAMILA; BICEGO, KENIA CARDOSO. Hypothalamic TRPV4 channels participate in the medial preoptic activation of warmth-defence responses in Wistar male rats. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, v. 471, n. 9, p. 1191-1203, . (12/15298-2, 15/04849-6, 11/19131-2, 17/17278-2, 15/02991-0)
ZENA, LUCAS A.; DILLON, DANIELLE; HUNT, KATHLEEN E.; NAVAS, CARLOS A.; BICEGO, KENIA C.; BUCK, C. LOREN. easonal changes in steroid and thyroid hormone content in shed skins of the tegu lizard Salvator meriana. JOURNAL OF COMPARATIVE PHYSIOLOGY B-BIOCHEMICAL SYSTEMIC AND ENVIRONMENTAL, v. 192, n. 1, . (14/16320-7, 17/01652-2, 18/06192-2, 15/04849-6)
MADELAIRE, CARLA B.; ZENA, LUCAS A.; DILLON, DANIELLE; SILVA, DIEGO P.; HUNT, KATHLEEN E.; BUCK, C. LOREN; BICEGO, KENIA C.; GOMES, FERNANDO R.. ho Rules Over Immunology? Seasonal Variation in Body Temperature, Steroid Hormones, and Immune Variables in a Tegu Lizar. INTEGRATIVE AND COMPARATIVE BIOLOGY, v. 61, n. 5, p. 1867-1880, . (12/24206-4, 18/00406-0, 15/04849-6, 14/16320-7, 19/13164-8, 17/01652-2)
CRISTINA-SILVA, CAROLINE; MARTINS, VICTOR; GARGAGLIONI, LUCIANE H.; BICEGO, KENIA C.. Mu and kappa opioid receptors of the periaqueductal gray stimulate and inhibit thermogenesis, respectively, during psychological stress in rats. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, v. 469, n. 9, p. 1151-1161, . (13/02813-9, 15/04849-6)

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