TRPV1 analgesics disturb core body temperature via a biased allosteric mechanism involving conformations distinct from that for nociception.

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期刊论文

作者：

Huang, Yi-Zhe;Ma, Jing-Xian;Bian, Yu-Jing;Bai, Qin-Ru;Gao, Yu-Hao;...

通讯作者：

Sun, Meng-Yang;Yu, Ye

作者机构：

[Gao, Yu-Hao; Di, Shu-Ke; Ma, Jing-Xian; Shao, Chang-Yan; Bai, Qin-Ru; Bian, Yu-Jing; Wang, Wen-Hui; Lei, Yun-Tao; Huang, Yi-Zhe] Schools of Basic Medicine and Clinical Pharmacy and Traditional Chinese Pharmacy, and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China

[Yang, Hui] Tea Research Institute, Hunan Academy of Agricultural Sciences, Changsha 410125, Hunan, China

[Yang, Xiao-Na] College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha 410128, China

[Cao, Peng] Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China

[Li, Chang-Zhu] State Key Laboratory of Utilization of Woody Oil Resource, Hunan Academy of Forestry, Changsha 410004, Hunan, China

通讯机构：

[Yu, Ye; Sun, Meng-Yang] S

Schools of Basic Medicine and Clinical Pharmacy and Traditional Chinese Pharmacy, and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China. Electronic address:

语种：

英文

关键词：

S4-S5 linker domain;TRP-box domain;TRPV1 analgesics;biased allosteric mechanism;core body temperature;hyperthermia;nociception

期刊：

Neuron

ISSN：

0896-6273

年：

2024

DOI：

10.1016/j.neuron.2024.02.016

机构署名：

本校为其他机构

院系归属：

生物科学技术学院

摘要：

Efforts on developing transient receptor potential vanilloid 1 (TRPV1) drugs for pain management have been hampered by deleterious hypo- or hyperthermia caused by TRPV1 agonists/antagonists. Here, we compared the effects of four antagonists on TRPV1 polymodal gating and core body temperature (CBT) in Trpv1(+/+), Trpv1(-/-), and Trpv1(T634A/T634A). Neither the effect on proton gating nor drug administration route, hair coverage, CBT rhythmic fluctuations, or inflammation had any influence on the differential actions of TRPV1 drugs on CBT. We identified the S4-S5 linker region exposed to the van...

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TRPV1 analgesics disturb core body temperature via a biased allosteric mechanism involving conformations distinct from that for nociception.

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