Adenosine A1 receptor potentiated glycinergic transmission in spinal cord dorsal horn of rats after peripheral inflammation
Adenosine A1 receptor potentiated glycinergic transmission in spinal cord dorsal horn of rats after peripheral inflammation
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腺苷 A1 受体增强周围炎症后大鼠脊髓背角的甘氨酸传递
DOI：
10.1016/j.neuropharm.2017.09.001
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发表时间：
2017-11-01
影响因子：
4.7
通讯作者：
Hu, Xiao-Dong
中科院分区：
文献类型：
--
作者：
Bai, Hu-Hu;Liu, Jiang-Ping;Hu, Xiao-Dong
腺苷存在于脊髓背角内的细胞外空间，并参与伤害性感觉信号的处理。外源性腺苷的全身或脊髓给药产生对病理性疼痛的有效镇痛作用。在这里，我们发现抑制性甘氨酸能神经传递是腺苷调节的重要靶点。在完整大鼠的脊髓切片中，腺苷增加了由甘氨酸受体（GlyRs）介导的抑制性突触后电流。在完全弗氏佐剂注射大鼠的脊髓切片中，腺苷增强甘氨酸能传递的程度高于对照大鼠。这种突触增强依赖于腺苷A1受体（A1 R）的激活，并归因于突触后GlyRs功能的改变。Gi蛋白偶联的A1 R通常通过G α 1/cAMP依赖性蛋白激酶（PKA）和G β γ途径发出信号。我们发现，阻断G α i/PKA或G β γ信号传导减弱了腺苷增加发炎大鼠甘氨酸能突触反应的能力。为了确定哪个GlyRs亚基受到A1 R的调节，我们记录了甘氨酸诱发的HEK 293 T细胞中的全细胞电流，该细胞共转染有A1 R和不同的GlyRs亚基。我们发现，α 1，最丰富的功能GlyRs亚基在成人脊髓，是不敏感的A1 R激活。然而，当GlyRs α 3亚基或α 1（ins）亚基（一种较长的α 1亚型）与A1 R共表达时，腺苷引起甘氨酸能电流显著增加。PKA和G β γ的抑制分别消除了A1 R对α 3和α 1（ins）的刺激作用。提示A1 R可能通过G α 1/PKA/α 3和G β γ/α 1（ins）途径增强炎症大鼠的甘氨酸能传递。(C)2017由Elsevier Ltd.出版
Adenosine is present at the extracellular space within spinal cord dorsal horn and engaged in the processing of nociceptive sensory signals. Systemic or spinal administration of exogenous adenosine produces a potent analgesia against pathological pain. Here we found that inhibitory glycinergic neurotransmission was an important target for adenosine regulation. In spinal cord slices from intact rats, adenosine increased the inhibitory postsynaptic currents mediated by glycine receptors (GlyRs). In spinal slices from Complete Freund's Adjuvant-injected rats, adenosine potentiated glycinergic transmission to a more degree than in control rats. This synaptic potentiation was dependent on the activation of adenosine A1 receptor (A1R), and attributed to the modification of postsynaptic GlyRs function. The Gi protein-coupled A1R typically signals through G alpha i/cAMP-dependent protein kinase (PKA) and G beta gamma pathways. We found that blockade of either G alpha i/PKA or G beta gamma signaling attenuated the ability of adenosine to increase glycinergic synaptic responses in inflamed rats. To identify which GlyRs subunit was subjected to A1R regulation, we recorded glycine-evoked whole-cell currents in HEK293T cells co-transfected with A1R and distinct GlyRs subunit. We found that alpha 1, the most abundant functional GlyRs subunit in adult spinal cord, was insensitive to A1R activation. However, when GlyRs alpha 3 subunit or alpha 1(ins) subunit, a longer alpha 1 isoform, was co-expressed with A1R, adenosine caused a significant increase of glycinergic currents. Inhibition of PKA and G beta gamma abolished the stimulatory effects of A1R on alpha 3 and alpha 1(ins), respectively. These data suggested that A1R might potentiate glycinergic transmission through G alpha i/PKA/alpha 3 and G beta gamma/alpha 1(ins) pathways in inflamed rat. (C) 2017 Published by Elsevier Ltd.