Green C B, Cahill G M, Besharse J C
Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City 66160-7400, USA.
Brain Res. 1995 Apr 24;677(2):283-90. doi: 10.1016/0006-8993(95)00166-n.
Many aspects of retinal physiology are controlled by a circadian clock including at least two steps in the melatonin synthetic pathway: the activity of the enzyme, N-acetyltransferase (NAT), and mRNA levels of the rate-limiting enzyme trytophan hydroxylase (TPH). Light and dopamine (through D2-like dopamine receptors) can phase shift the clock, and can also acutely inhibit NAT activity, resulting in supressed melatonin synthesis. In this paper, we show that eyecups cultured in constant darkness maintain a clock-controlled rhythm in TPH mRNA, with low levels in early day, rising to a peak in early night. Both eyecups and isolated retinas, cultured in light during the day, also exhibit a similar increase in TPH mRNA levels, indicating that this expression is not acutely inhibited by light. Treatment with light or quinpirole (D2 dopamine receptor agonist) in early night, at a time and dose that acutely inhibits NAT activity, does not change levels of TPH mRNA. Addition of eticlopride (D2 dopamine receptor antagonist) during the day, also has no effect on the normal daytime increase in TPH message levels. Therefore, TPH mRNA level is controlled by a circadian clock located within the eye, but acute effects of light or dopamine are not detected.
视网膜生理学的许多方面受昼夜节律时钟控制，包括褪黑素合成途径中的至少两个步骤：N-乙酰转移酶（NAT）的活性以及限速酶色氨酸羟化酶（TPH）的mRNA水平。光和多巴胺（通过D2样多巴胺受体）可使生物钟发生相位偏移，还可急性抑制NAT活性，导致褪黑素合成受抑制。在本文中，我们表明在持续黑暗中培养的眼杯在TPH mRNA中维持一种受时钟控制的节律，在白天早期水平较低，在夜晚早期升至峰值。在白天光照下培养的眼杯和分离的视网膜也表现出TPH mRNA水平的类似增加，表明这种表达不受光的急性抑制。在夜晚早期，以急性抑制NAT活性的时间和剂量用光或喹吡罗（D2多巴胺受体激动剂）处理，不会改变TPH mRNA的水平。在白天添加阿立必利（D2多巴胺受体拮抗剂），对TPH信息水平的正常白天增加也没有影响。因此，TPH mRNA水平受眼内生物钟控制，但未检测到光或多巴胺的急性作用。
