@article{574c3e2710f84dea9ce2ab204ad155e8,
title = "The hypothermic effect of hydrogen sulfide is mediated by the transient receptor potential ankyrin-1 channel in mice",
abstract = "Hydrogen sulfide (H2S) has been shown in previous studies to cause hypothermia and hy-pometabolism in mice, and its thermoregulatory effects were subsequently investigated. However, the molecular target through which H2S triggers its effects on deep body temperature has remained un-known. We investigated the thermoregulatory response to fast-(Na2S) and slow-releasing (GYY4137) H2S donors in C57BL/6 mice, and then tested whether their effects depend on the transient receptor potential ankyrin-1 (TRPA1) channel in Trpa1 knockout (Trpa1−/−) and wild-type (Trpa1+/+) mice. Intracerebroventricular administration of Na2S (0.5–1 mg/kg) caused hypothermia in C57BL/6 mice, which was mediated by cutaneous vasodilation and decreased thermogenesis. In contrast, intraperitoneal administration of Na2S (5 mg/kg) did not cause any thermoregulatory effect. Central administration of GYY4137 (3 mg/kg) also caused hypothermia and hypometabolism. The hypothermic response to both H2S donors was significantly (p < 0.001) attenuated in Trpa1−/− mice compared to their Trpa1+/+ littermates. Trpa1 mRNA transcripts could be detected with RNAscope in hypothalamic and other brain neurons within the autonomic thermoeffector pathways. In con-clusion, slow-and fast-releasing H2S donors induce hypothermia through hypometabolism and cutaneous vasodilation in mice that is mediated by TRPA1 channels located in the brain, presumably in hypothalamic neurons within the autonomic thermoeffector pathways.",
keywords = "GYY4137, HS, Hypothermia, Thermoregulation, TRPA1",
author = "Emoke Olah and Zoltan Rumbus and Viktoria Kormos and Valeria Tekus and Eszter Pakai and Wilson, {Hannah V.} and Kata Fekete and Margit Solymar and Leonardo Kelava and Patrik Keringer and Balazs Gaszner and Matthew Whiteman and Julie Keeble and Erika Pinter and Andras Garami",
note = "Funding Information: This work was supported by the National Research, Development and Innovation Office (FK 124483 to A.G.), the Medical School, University of Pecs (KA-2019-27 to A.G.), the New National Excellence Program of the Hungarian Ministry for Innovation and Technology (UNKP-20-3-II-PTE-877 and UNKP-21-3-II-PTE-1317 to Z.R.), the Higher Education Institutional Excellence Program of the Ministry of Human Capacities in Hungary (20765-3/2018/FEKUTSTRAT to A.G.), and the European Union, co-financed by the European Social Fund (EFOP-3.6.1-16-2016-00004 to B.G. and A.G.). A.G. acknowledges the Janos Bolyai Scholarship of the Hungarian Academy of Sciences. B.G. was funded by the National Research, Development and Innovation Fund of Hungary, financed under the 2020-4.1.1-TKP2020 funding scheme (Project No: TKP2020-IKA-08); NAP 2017-1.2.1-NKP-2017-00002; GINOP-2.3.2-15-2016-00050; MTA-TKI14016; EFOP-3.6.3-VEKOP-16-2017-00009; and EFOP-3.6.2-16-2017-00008. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Acknowledgments: The authors are grateful to Roghiyah Riahi for her help with the thermoregula-tory experiments and to Aniko Varnagyne Rozsafi for her excellent technical assistance. Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2021",
month = oct,
doi = "10.3390/ph14100992",
language = "English",
volume = "14",
journal = "Pharmaceuticals",
issn = "1424-8247",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "10",
}