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光对视网膜多巴胺生物合成及酪氨酸羟化酶活性的调节

Regulation of retinal dopamine biosynthesis and tyrosine hydroxylase activity by light.

作者信息

Iuvone P M

出版信息

Fed Proc. 1984 Sep;43(12):2709-13.

PMID:6147273
Abstract

Dopamine (DA)-containing neurons of the rat retina are apparently activated transsynaptically by photic stimulation. Exposure of dark-adapted rats to light increases retinal DA biosynthesis and metabolism. Associated with the light-evoked increase of DA biosynthesis is a rapid activation of tyrosine hydroxylase (TH), the rate-limiting enzyme of catecholamine biosynthesis. The activation of TH is characterized by an increased affinity of the enzyme for the pteridine cofactor. Because TH in dark-adapted retinas is apparently not saturated with cofactor, the light-evoked increase of affinity is probably responsible for the observed stimulation of DA biosynthesis. Cyclic AMP (cAMP)-dependent protein phosphorylation in vitro activates TH extracted from dark-adapted retinas, and phosphorylation-induced TH activation is very similar and not additive with light-evoked activation of the enzyme. Incubation of viable cell suspensions of dissociated retinas with 8-bromo cAMP also activates TH, which indicates the availability of sufficient cAMP-dependent protein kinase in the proper subcellular compartment to regulate the enzyme in situ. The DA-containing neurons of the rat retina are tonically inhibited in darkness, and evidence is presented that this tonic inhibition involves direct synaptic input to the DA neurons from gamma-aminobutyric acid-containing amacrine cells. The DA-containing neurons are also subject to feedback inhibition through DA receptors, and to modulation by alpha 2-adrenergic receptors.

摘要

大鼠视网膜中含多巴胺(DA)的神经元显然通过光刺激被跨突触激活。将暗适应的大鼠暴露于光下会增加视网膜DA的生物合成和代谢。与光诱发的DA生物合成增加相关的是酪氨酸羟化酶(TH)的快速激活,酪氨酸羟化酶是儿茶酚胺生物合成的限速酶。TH的激活表现为该酶对蝶啶辅因子的亲和力增加。由于暗适应视网膜中的TH显然没有被辅因子饱和,光诱发的亲和力增加可能是观察到的DA生物合成刺激的原因。体外依赖环磷酸腺苷(cAMP)的蛋白磷酸化可激活从暗适应视网膜中提取的TH,磷酸化诱导的TH激活与该酶的光诱发激活非常相似且无叠加效应。用8-溴cAMP孵育解离视网膜的活细胞悬液也可激活TH,这表明在适当的亚细胞区室中有足够的依赖cAMP的蛋白激酶来原位调节该酶。大鼠视网膜中含DA的神经元在黑暗中受到紧张性抑制,有证据表明这种紧张性抑制涉及来自含γ-氨基丁酸的无长突细胞对DA神经元的直接突触输入。含DA的神经元也受到通过DA受体的反馈抑制以及α2-肾上腺素能受体的调节。

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