Departments of Anesthesia, University of Iowa, USA.
Departments of Pharmacology, University of Iowa, USA.
Mol Pain. 2017 Jan-Dec;13:1744806917715210. doi: 10.1177/1744806917715210.
A diverse array of G protein-coupled receptors (GPCRs) is implicated in the modulation of nociception. The efficacy and potency of several GPCR agonists change as a consequence of peripheral inflammatory injury. Whether these changes reflect alterations in expression of the G proteins themselves is not known. This study examined the expression of transcripts and proteins for the α subunits of three classes of heteromeric G proteins in the dorsal horn of the spinal cord and the rostral ventromedial medulla (RVM) of male rats four days and two weeks after intraplantar injection of complete Freund’s adjuvant (CFA) or saline. Levels of Gα transcript in the dorsal horn or RVM were unchanged by CFA treatment. However, in the dorsal horn, Gαi protein decreased in cytosolic and membrane fractions four days after CFA treatment. Levels of Gαz protein decreased in the membrane fraction. Levels of the other Gα subunits did not differ. Levels of the Gα subunits were unchanged two weeks after CFA treatment. In the RVM, Gαz protein levels decreased in the cytosolic fraction four days after CFA treatment. No other differences were observed. Two weeks after CFA, the levels for all Gα subunits trended higher in the RVM. These data indicate that peripheral inflammatory injury induces subtle changes in the abundance of Gα subunits that is specific with respect to class, subcellular compartment, tissue, and time after injury. These changes have the potential to alter the balance of the different subcellular signaling pathways through which GPCR agonists act to modulate nociception.
多种 G 蛋白偶联受体(GPCR)被认为参与了痛觉调制。几种 GPCR 激动剂的效力和效价会因外周炎症损伤而发生变化。这些变化是否反映了 G 蛋白本身表达的改变尚不清楚。本研究在雄性大鼠足底注射完全弗氏佐剂(CFA)或生理盐水 4 天和 2 周后,检测了脊髓背角和延髓头端腹内侧区(RVM)中三种异源三聚体 G 蛋白的α亚基的转录本和蛋白的表达。CFA 处理对背角或 RVM 中的 Gα 转录水平没有影响。然而,在背角中,CFA 处理 4 天后,胞质和膜部分的 Gαi 蛋白减少。Gαz 蛋白在膜部分的水平降低。其他 Gα 亚基的水平没有差异。CFA 处理 2 周后,Gα 亚基的水平没有变化。在 RVM 中,CFA 处理 4 天后,胞质部分的 Gαz 蛋白水平降低。没有观察到其他差异。CFA 处理 2 周后,RVM 中所有 Gα 亚基的水平都呈上升趋势。这些数据表明,外周炎症损伤诱导了 Gα 亚基丰度的微妙变化,这种变化在类别、亚细胞区室、组织和损伤后时间上具有特异性。这些变化有可能改变 GPCR 激动剂调节痛觉的不同亚细胞信号通路之间的平衡。
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