GINIP, a Gαi-interacting protein, functions as a key modulator of peripheral GABAB receptor-mediated analgesia.
GINIP, a Gαi-interacting protein, functions as a key modulator of peripheral GABAB receptor-mediated analgesia.
复制标题
DOI：
10.1016/j.neuron.2014.08.056
复制
发表时间：
2014-10-01
期刊：
影响因子：
16.2
通讯作者：
Moqrich A
中科院分区：
文献类型：
--
作者：
Gaillard S;Lo Re L;Mantilleri A;Hepp R;Urien L;Malapert P;Alonso S;Deage M;Kambrun C;Landry M;Low SA;Alloui A;Lambolez B;Scherrer G;Le Feuvre Y;Bourinet E;Moqrich A
神经性疼痛的一个特征是GABA能抑制功能降低。伤害感受器在这一过程中起着关键作用。然而，背后的伤害感受器介导的GABA信号调制的机制仍有待阐明。在这里，我们描述了GINIP的鉴定，GINIP是一种在两种不同的非肽能伤害感受器亚群中表达的Gα i相互作用蛋白。GINIP敲除小鼠在炎症和神经病变模型中产生选择性和长期机械超敏反应。GINIP基因敲除小鼠对GABAB的反应性受损，但对δ或μ阿片受体激动剂介导的镇痛反应性不受损，特别是在备用神经损伤（SNI）模型中。一致的，GINIP缺陷背根神经节神经元有较低的高电压激活的钙通道和缺陷的突触前抑制板IIi中间神经元的突触前抑制诱发的抑制。这些结果进一步支持了无髓鞘C纤维在损伤诱导的脊髓GABA能抑制调节中的作用，并将GINIP鉴定为外周诱发的GABA受体信号传导的关键调节剂。
One feature of neuropathic pain is a reduced GABAergic inhibitory function. Nociceptors have been suggested to play a key role in this process. However, the mechanisms behind nociceptor-mediated modulation of GABA signaling remain to be elucidated. Here we describe the identification of GINIP, a Gαi-interacting protein expressed in two distinct subsets of nonpeptidergic nociceptors. GINIP null mice develop a selective and prolonged mechanical hypersensitivity in models of inflammation and neuropathy. GINIP null mice show impaired responsiveness to GABAB, but not to delta or mu opioid receptor agonist-mediated analgesia specifically in the spared nerve injury (SNI) model. Consistently, GINIP-deficient dorsal root ganglia neurons had lower baclofen-evoked inhibition of high-voltage-activated calcium channels and a defective presynaptic inhibition of lamina IIi interneurons. These results further support the role of unmyelinated C fibers in injury-induced modulation of spinal GABAergic inhibition and identify GINIP as a key modulator of peripherally evoked GABAB-receptors signaling.
登录
查看更多内容
影响因子：
64.5
作者：
Li L;Rutlin M;Abraira VE;Cassidy C;Kus L;Gong S;Jankowski MP;Luo W;Heintz N;Koerber HR;Woodbury CJ;Ginty DD
通讯作者：
Ginty DD
影响因子：
64.8
作者：
Jasmin, L;Rabkin, SD;Ohara, PT
通讯作者：
Ohara, PT
影响因子：
16.2
作者：
Bardoni R;Tawfik VL;Wang D;François A;Solorzano C;Shuster SA;Choudhury P;Betelli C;Cassidy C;Smith K;de Nooij JC;Mennicken F;O'Donnell D;Kieffer BL;Woodbury CJ;Basbaum AI;MacDermott AB;Scherrer G
通讯作者：
Scherrer G
影响因子：
3.3
作者：
Gangadharan V;Agarwal N;Brugger S;Tegeder I;Bettler B;Kuner R;Kurejova M
通讯作者：
Kurejova M
影响因子：
25
作者：
Han, Liang;Ma, Chao;Liu, Qin;Weng, Hao-Jui;Cui, Yiyuan;Tang, Zongxiang;Kim, Yushin;Nie, Hong;Qu, Lintao;Patel, Kush N.;Li, Zhe;McNeil, Benjamin;He, Shaoqiu;Guan, Yun;Xiao, Bo;LaMotte, Robert H.;Dong, Xinzhong
通讯作者：
Dong, Xinzhong