Elliott K J, Todd Weber E, Rea M A
Department of Biology and Biochemistry, University of Houston, Houston, TX 77204-5513, USA.
Eur J Pharmacol. 2001 Feb 23;414(1):45-53. doi: 10.1016/s0014-2999(01)00786-5.
Circadian rhythms are synchronized to the environmental light-dark cycle by daily, light-induced adjustments in the phase of a biological clock located in the suprachiasmatic nucleus. Ambient light alters the phase of the clock via a direct, glutamatergic projection from retinal ganglion cells. We investigated the hypothesis that adenosine A1 receptors modulate the phase adjusting effect of light on the circadian clock. Systemic administration of the selective adenosine A1 receptor agonist, N6-cyclohexyladenosine (CHA), significantly (p<0.05) attenuated light-induced phase delays and advances of the circadian activity rhythm. Selective agonists for the adenosine A2A and adenosine A3 receptors were without effect. The inhibitory effect of CHA on light-induced phase advances was dose-dependent (0.025-1.0 mg/kg, ED(50)=0.3 mg/kg), and this effect was blocked in a dose-dependent (0.005-1.0 mg/kg) manner by the adenosine A1 receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). Injection of CHA (10 microM) into the region of the suprachiasmatic nucleus significantly attenuated light-induced phase advances, and this effect was also blocked by DPCPX (100 microM). The results suggest that adenosine A1 receptors located in the region of the suprachiasmatic nucleus regulate the response of the circadian clock to the phase-adjusting effects of light.
昼夜节律通过位于视交叉上核的生物钟相位的每日光诱导调整，与环境明暗周期同步。环境光通过视网膜神经节细胞的直接谷氨酸能投射改变生物钟的相位。我们研究了腺苷A1受体调节光对昼夜节律钟相位调整作用的假说。选择性腺苷A1受体激动剂N6-环己基腺苷（CHA）的全身给药显著（p<0.05）减弱了光诱导的昼夜活动节律的相位延迟和提前。腺苷A2A和腺苷A3受体的选择性激动剂没有效果。CHA对光诱导的相位提前的抑制作用是剂量依赖性的（0.025-1.0mg/kg，ED(50)=0.3mg/kg），并且这种作用被腺苷A1受体拮抗剂8-环戊基-1,3-二丙基黄嘌呤（DPCPX）以剂量依赖性（0.005-1.0mg/kg）的方式阻断。向视交叉上核区域注射CHA（10μM）显著减弱了光诱导的相位提前，并且这种作用也被DPCPX（100μM）阻断。结果表明，位于视交叉上核区域的腺苷A1受体调节昼夜节律钟对光相位调整作用的反应。
