Lao L-J, Kawasaki Y, Yang K, Fujita T, Kumamoto E
Department of Physiology, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan.
Neuroscience. 2004;125(1):221-31. doi: 10.1016/j.neuroscience.2004.01.029.
The present study examined the actions of adenosine on monosynaptic Adelta and C primary-afferent excitatory postsynaptic currents (EPSCs) recorded from substantia gelatinosa (SG) neurons of an adult rat spinal cord slice. In 67% of the neurons examined, adenosine reversibly decreased the amplitude of the Adelta-fiber EPSC, while in 13% of the neurons the amplitude was reduced or unaffected, which was followed by its increase persisting for several minutes after adenosine washout. The remaining neurons did not exhibit a change in the amplitude. The reduction in Adelta-fiber EPSC amplitude by adenosine was dose-dependent with an effective concentration for half-inhibition (EC50) value of 217 microM. When examined by using a paired-pulse stimulus, a ratio of the second to first Adelta-fiber EPSC amplitude under the reduction was larger than that of EPSC amplitude in the control, suggesting a presynaptic action of adenosine. In 69% of the neurons tested, the C-fiber EPSC was reversibly decreased in amplitude by adenosine (100 microM) by an extent comparable to that of Adelta-fiber EPSC; the remaining neurons were without adenosine actions. Similar inhibitory actions of adenosine were also seen in neurons where both Adelta-fiber and C-fiber EPSCs were elicited. Similar reduction in the Adelta-fiber or C-fiber EPSC amplitude was induced by an A1 adenosine-receptor agonist, N6-cyclopentyladenosine (1 microM), and the adenosine-induced reduction was not observed in the presence of an A1 antagonist, 8-cyclopentyl-1,3-dipropylxanthine (1 microM). An A2a agonist, CGS 21680 (1 microM), did not significantly affect the Adelta-fiber EPSC amplitude. It is concluded that adenosine presynaptically inhibits monosynaptic Adelta-fiber and C-fiber transmission by a similar extent through the activation of the A1 receptor in many but not all SG neurons; this could contribute to at least a part of antinociception by intrathecally administered adenosine analogues and probably by endogenous adenosine.
本研究检测了腺苷对成年大鼠脊髓切片胶状质（SG）神经元记录的单突触Aδ和C初级传入兴奋性突触后电流（EPSC）的作用。在67%的被检测神经元中，腺苷可逆性降低Aδ纤维EPSC的幅度，而在13%的神经元中，幅度降低或未受影响，随后在腺苷洗脱后其幅度持续增加数分钟。其余神经元的幅度未出现变化。腺苷对Aδ纤维EPSC幅度的降低呈剂量依赖性，半数抑制有效浓度（EC50）值为217μM。当采用双脉冲刺激进行检测时，在幅度降低情况下第二个与第一个Aδ纤维EPSC幅度的比值大于对照组EPSC幅度的比值，提示腺苷具有突触前作用。在69%的被检测神经元中，腺苷（100μM）使C纤维EPSC幅度可逆性降低，降低程度与Aδ纤维EPSC相当；其余神经元未出现腺苷作用。在同时引发Aδ纤维和C纤维EPSC的神经元中也观察到腺苷的类似抑制作用。A1腺苷受体激动剂N6-环戊基腺苷（1μM）诱导Aδ纤维或C纤维EPSC幅度出现类似降低，而在存在A1拮抗剂8-环戊基-1,3-二丙基黄嘌呤（1μM）时未观察到腺苷诱导的降低。A2a激动剂CGS 21680（1μM）对Aδ纤维EPSC幅度无显著影响。得出结论，在许多但并非所有的SG神经元中，腺苷通过激活A1受体在突触前以类似程度抑制单突触Aδ纤维和C纤维传递；这可能至少部分解释了鞘内注射腺苷类似物以及可能内源性腺苷产生的镇痛作用。
