Proll M A, Morgan W W
J Pharmacol Exp Ther. 1983 Dec;227(3):627-32.
The effects of inhibiting gamma-aminobutyric acid-transaminase (GABA-T) with aminooxyacetic acid or with gabaculine and inhibiting GABA uptake with nipecotic acid on dopamine (DA) synthesis in the retina of light-exposed rats were studied. 3,4-Dihydroxyphenylalanine (Dopa) accumulation after the inhibition of L-aromatic amino acid decarboxylase with NSD-1015 was used as an index of DA synthesis. The GABA-T inhibitors significantly increased GABA levels in the retina but had no effect on retinal Dopa accumulation in the light. Dopa accumulation was significantly inhibited at a high dosage by nipecotic acid alone and by low dosages of nipecotic acid in rats pretreated with either aminooxyacetic acid or gabaculine. The dosages of nipecotic acid which inhibited Dopa accumulation in the light also inhibited [3H]GABA uptake in the retina. The inhibitory effects of gabaculine and nipecotic acid on Dopa accumulation appeared to occur at least partially via GABA receptors because their action was significantly reversed by the GABA antagonist bicuculline methiodide. These experiments thus suggest that endogenous GABA can suppress the light-evoked increase in DA synthesis in the rat retina and support previous studies which concluded that an inhibitory GABA input may at least partially regulate the activity of the DA neurons in the retina of rats.
研究了用氨氧乙酸或加巴喷丁抑制γ-氨基丁酸转氨酶(GABA-T)以及用尼克酸抑制GABA摄取对光暴露大鼠视网膜中多巴胺(DA)合成的影响。用NSD-1015抑制L-芳香族氨基酸脱羧酶后3,4-二羟基苯丙氨酸(多巴)的积累用作DA合成的指标。GABA-T抑制剂显著提高了视网膜中的GABA水平,但对光照下视网膜多巴的积累没有影响。单独使用尼克酸高剂量以及在预先用氨氧乙酸或加巴喷丁处理的大鼠中使用低剂量尼克酸时,多巴积累均受到显著抑制。在光照下抑制多巴积累的尼克酸剂量也抑制了视网膜中[3H]GABA的摄取。加巴喷丁和尼克酸对多巴积累的抑制作用似乎至少部分通过GABA受体发生,因为它们的作用被GABA拮抗剂甲硫双环己哌啶显著逆转。因此,这些实验表明内源性GABA可以抑制大鼠视网膜中光诱发的DA合成增加,并支持先前的研究,该研究得出结论,抑制性GABA输入可能至少部分调节大鼠视网膜中DA神经元的活性。