Watanabe A, Moriya T, Nisikawa Y, Araki T, Hamada T, Shibata S, Watanabe S
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Brain Res. 1996 Nov 18;740(1-2):329-36. doi: 10.1016/s0006-8993(96)00881-5.
Adenosine is widely accepted to act as an inhibitory neuromodulator in the mammalian central nervous system. In the present study, we examined whether adenosine receptor agonist modifies the photic entraining responses in the rat suprachiasmatic nucleus both in vivo and in vitro. Light (200 lux, 15 min)-induced phase shifts of hamster wheel-running rhythms was attenuated by a systemic administration of A1-adenosine receptor agonist N6-cyclohexyladenosine (N-CHA) in a dose-dependent manner; 0.5 mg/kg N-CHA caused 60% inhibition of light-induced phase shifts. On the other hand, A2-adenosine receptor agonist N6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)-ethyl]adenosine (DPMA) failed to inhibit light-induced phase shifts. Systemic administration of N-CHA but not of DPMA inhibited light (300 lux, 1 h)-induced Fos expression in the suprachiasmatic nucleus in a dose-dependent manner; 1 mg/kg N-CHA caused 73% inhibition of light-induced Fos expression. Bath application of N-CHA but not of DPMA inhibited optic nerve stimulation-evoked field potentials in rat suprachiasmatic nucleus slices. The present results suggest that activation of adenosine A1-receptor attenuates the photic input through the inhibition of retinohypotalamic pathway to the SCN.
腺苷被广泛认为在哺乳动物中枢神经系统中作为一种抑制性神经调质发挥作用。在本研究中，我们检测了腺苷受体激动剂在体内和体外是否会改变大鼠视交叉上核中的光诱导同步反应。全身性给予A1-腺苷受体激动剂N6-环己基腺苷（N-CHA）可呈剂量依赖性减弱光（200勒克斯，15分钟）诱导的仓鼠转轮节律的相位偏移；0.5毫克/千克的N-CHA可导致光诱导相位偏移受到60%的抑制。另一方面，A2-腺苷受体激动剂N6-[2-(3,5-二甲氧基苯基)-2-(2-甲基苯基)-乙基]腺苷（DPMA）未能抑制光诱导的相位偏移。全身性给予N-CHA而非DPMA可呈剂量依赖性抑制光（300勒克斯，1小时）诱导的视交叉上核中的Fos表达；1毫克/千克的N-CHA可导致光诱导的Fos表达受到73%的抑制。在大鼠视交叉上核切片中，浴用N-CHA而非DPMA可抑制视神经刺激诱发的场电位。目前的结果表明，腺苷A1受体的激活通过抑制视网膜下丘脑通路至视交叉上核来减弱光输入。
