文献类型：期刊文献

英文题名：GPR39 regulated spinal glycinergic inhibition and mechanical inflammatory pain

作者：Bai, Hu-Hu[1,2];Wang, Kang-Li[1];Zeng, Xiang-Ru[1];Li, Jing[1];Li, Yuan[1];Xu, Jia-Yu[1];Zhang, Yue[3];Jiang, Hai-Feng[3];Yang, Xian[1];Suo, Zhan-Wei[1];Hu, Xiao-Dong[1]

第一作者：Bai, Hu-Hu

通信作者：Hu, XD[1]

机构：[1]Lanzhou Univ, Sch Pharm, Dept Mol Pharmacol, Lanzhou 730000, Gansu, Peoples R China;[2]Lanzhou Univ, Sch Life Sci, Lanzhou 730000, Gansu, Peoples R China;[3]Gansu Univ Chinese Med, Sch Publ Hlth, Lanzhou 730000, Gansu, Peoples R China

第一机构：Lanzhou Univ, Sch Pharm, Dept Mol Pharmacol, Lanzhou 730000, Gansu, Peoples R China

通信机构：[1]corresponding author), Lanzhou Univ, Sch Pharm, Dept Mol Pharmacol, Lanzhou 730000, Gansu, Peoples R China.

年份：2024

卷号：10

期号：5

外文期刊名：SCIENCE ADVANCES

收录：;EI(收录号：20240715558277);Scopus(收录号：2-s2.0-85183790897);WOS:【SCI-EXPANDED(收录号:WOS:001186784700008)】；

基金：This work was supported by the National Natural Science Foundation of China grants 81973296 (to X.- D.H.), 32170997 (to X.- D.H.), and 82073822 (to Z.-W.S.) and School of Pharmacy and State Key Laboratory of Applied Organic Chemistry, Lanzhou University, P.R. China.

语种：英文

外文关键词：Amino acids - Proteins

摘要：G protein-coupled receptor 39 (GPR39) senses the change of extracellular divalent zinc ion and signals through multiple G proteins to a broad spectrum of downstream effectors. Here, we found that GPR39 was prevalent at inhibitory synapses of spinal cord somatostatin-positive (SOM+) interneurons, a mechanosensitive subpopulation that is critical for the conveyance of mechanical pain. GPR39 complexed specifically with inhibitory glycine receptors (GlyRs) and helped maintain glycinergic transmission in a manner independent of G protein signalings. Targeted knockdown of GPR39 in SOM+ interneurons reduced the glycinergic inhibition and facilitated the excitatory output from SOM+ interneurons to spinoparabrachial neurons that engaged superspinal neural circuits encoding both the sensory discriminative and affective motivational domains of pain experience. Our data showed that pharmacological activation of GPR39 or augmenting GPR39 interaction with GlyRs at the spinal level effectively alleviated the sensory and affective pain induced by complete Freund's adjuvant and implicated GPR39 as a promising therapeutic target for the treatment of inflammatory mechanical pain.