A circadian clock in the fish retina regulates dopamine release via activation of melatonin receptors
A circadian clock in the fish retina regulates dopamine release via activation of melatonin receptors
复制标题
DOI：
10.1113/jphysiol.2003.053710
复制
发表时间：
2004-01-15
影响因子：
5.5
通讯作者：
Mangel, SC
中科院分区：
文献类型：
--
作者：
Ribelayga, C;Wang, Y;Mangel, SC
尽管脊椎动物视网膜中的许多生化、形态和生理过程都是由昼夜节律（24小时）时钟控制的，但时钟的位置以及时钟如何改变视网膜功能尚不清楚。例如，一些观察结果表明，多巴胺（一种视网膜神经调节剂）可能在视网膜节律性中发挥重要作用，但多巴胺与位于视网膜内外的时钟之间的联系仍有待确定。我们发现，在连续黑暗中培养 56 小时的离体金鱼视网膜中，内源性多巴胺释放明显表现出主观日内高值的昼夜节律。培养基中持续存在的褪黑激素（1 nm）消除了多巴胺释放的昼夜节律，并使数值始终保持在较低水平并等于夜间数值。选择性褪黑激素拮抗剂鲁津吲哚（1 mum）也消除了多巴胺节律，但其值很高且与白天的值相同。在主观白天晚些时候使用褪黑激素引入了杆输入并减少了鱼锥水平细胞的视锥输入，这种状态通常在主观夜间观察到。相比之下，在主观夜间施用luzidole会减少视杆输入并增加视锥输入。先前应用多巴胺或螺哌隆（一种选择性多巴胺D-2样拮抗剂）分别阻断褪黑激素和luzidole的上述作用。这些发现表明，脊椎动物视网膜中的生物钟通过褪黑激素受体的激活来调节多巴胺的释放，并且内源性褪黑激素通过多巴胺介导的 D-2 样受体激活来调节视杆细胞和视锥细胞通路。
Although many biochemical, morphological and physiological processes in the vertebrate retina are controlled by a circadian (24 h) clock, the location of the clock and how the clock alters retinal function are unclear. For instance, several observations have suggested that dopamine, a retinal neuromodulator, may play an important role in retinal rhythmicity but the link between dopamine and a clock located within or outside the retina remains to be established. We found that endogenous dopamine release from isolated goldfish retinae cultured in continuous darkness for 56 h clearly exhibited a circadian rhythm with high values during the subjective day. The continuous presence of melatonin (1 nm) in the culture medium abolished the circadian rhythm of dopamine release and kept values constantly low and equal to the night-time values. The selective melatonin antagonist luzindole (1 mum) also abolished the dopamine rhythm but the values were high and equal to the daytime values. Melatonin application during the late subjective day introduced rod input and reduced cone input to fish cone horizontal cells, a state usually observed during the subjective night. In contrast, luzindole application during the subjective night decreased rod input and increased cone input. Prior application of dopamine or spiperone, a selective dopamine D-2-like antagonist, blocked the above effects of melatonin and luzindole, respectively. These findings indicate that a circadian clock in the vertebrate retina regulates dopamine release by the activation of melatonin receptors and that endogenous melatonin modulates rod and cone pathways through dopamine-mediated D-2-like receptor activation.