GPR39 regulated spinal glycinergic inhibition and mechanical inflammatory pain.
GPR39 regulated spinal glycinergic inhibition and mechanical inflammatory pain.
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DOI：
10.1126/sciadv.adj3808
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发表时间：
2024-02-02
期刊：
影响因子：
13.6
通讯作者：
Hu, Xiao-Dong
中科院分区：
文献类型：
--
作者：
Bai, Hu-Hu;Wang, Kang-Li;Zeng, Xiang-Ru;Li, Jing;Li, Yuan;Xu, Jia-Yu;Zhang, Yue;Jiang, Hai-Feng;Yang, Xian;Suo, Zhan-Wei;Hu, Xiao-Dong
G 蛋白偶联受体 39 (GPR39) 感知细胞外二价锌离子的变化，并通过多个 G 蛋白向广泛的下游效应器发出信号。在这里，我们发现 GPR39 在脊髓生长抑素阳性 (SOM+) 中间神经元的抑制性突触中普遍存在，这是一种机械敏感亚群，对于机械疼痛的传递至关重要。 GPR39 与抑制性甘氨酸受体 (GlyR) 特异性复合，并以独立于 G 蛋白信号传导的方式帮助维持甘氨酸能传递。 SOM+中间神经元中GPR39的靶向敲除减少了甘氨酸能抑制，并促进了SOM+中间神经元向脊髓旁臂神经元的兴奋性输出，这些神经元参与编码疼痛体验的感觉辨别和情感动机领域的超脊髓神经回路。我们的数据表明，GPR39的药理学激活或增强GPR39与GlyR在脊髓水平的相互作用可有效减轻弗氏完全佐剂引起的感觉和情感疼痛，并表明GPR39是治疗炎症性机械性疼痛的有前景的治疗靶点。 GPR39 参与脊髓甘氨酸能抑制生长抑素阳性中间神经元传递机械性疼痛。
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. GPR39 engages in spinal glycinergic inhibition of somatostatin-positive interneurons transmitting mechanical pain.
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DOI：
10.1073/pnas.2208541120
发表时间：
2023-01-03
影响因子：
11.1
作者：
通讯作者：
--
影响因子：
64.5
作者：
Duan B;Cheng L;Bourane S;Britz O;Padilla C;Garcia-Campmany L;Krashes M;Knowlton W;Velasquez T;Ren X;Ross S;Lowell BB;Wang Y;Goulding M;Ma Q
通讯作者：
Ma Q
影响因子：
16.2
作者：
Foster, Edmund;Wildner, Hendrik;Tudeau, Laetitia;Haueter, Sabine;Ralvenius, William T.;Jegen, Monika;Johannssen, Helge;Hoesli, Ladina;Haenraets, Karen;Ghanem, Alexander;Conzelmann, Karl-Klaus;Boesl, Michael;Zeilhofer, Hanns Ulrich
通讯作者：
Zeilhofer, Hanns Ulrich
DOI：
10.1002/trc2.12214
发表时间：
2021
期刊：
Alzheimer's & dementia (New York, N. Y.)
影响因子：
--
作者：
Davis CM;Bah TM;Zhang WH;Nelson JW;Golgotiu K;Nie X;Alkayed FN;Young JM;Woltjer RL;Silbert LC;Grafe MR;Alkayed NJ
通讯作者：
Alkayed NJ
影响因子：
64.5
作者：
Hanack, Christina;Moroni, Mirko;Siemens, Jan
通讯作者：
Siemens, Jan