Sachs C, Jonsson G, Heikkila R, Cohen G
Acta Physiol Scand. 1975 Mar;93(3):345-51. doi: 10.1111/j.1748-1716.1975.tb05823.x.
In vitro studies with the neurotoxic compounds 6-hydroxydopamine (6-OH-DA) and 6-aminodopamine (6-A-DA) showed that noradrenaline (NA) markedly inhibited the autooxidation of 6-OH-DA, but not of 6-A-DA. In vivo studies of the adrenergic nerves in rat iris showed that the neurotoxic potency of 6-OH-DA, but not 6-A-DA, was increased after NA depletion by alpha-methyl-p-tyrosine methylester (H44/68). Neurotoxicity was evaluated by measuring the associated decrease in 3-H-NA uptake. Intraocular injection of NA counteracted the degenerative action of 6-OH-DA in both untreated and H44/68 pretreated rats. Intraocular NA did not interfere with the neurotoxicity of 6-A-DA. Additionally, octopamine did not affect the rate of autooxidation nor the neurotoxic potency of 6-OH-DA or 6-A-DA. Control experiments with 3-H-6-OH-DA showed that the intraneuronal NA levels did not significantly affect the intraneuronal accumulation of 6-OH-DA. The parallelism between the in vitro results on autooxidation and in vivo data on neurotoxicity makes it appear that the neurotoxic potency of 6-OH-DA and 6-A-DA is closely associated with their rates of autooxidation. The control of the degenerative action of 6-OH-DA by intraneuronal NA may be mediated via reaction of NA with radicals formed from oxygen during autooxidation of 6-OH-DA.
使用神经毒性化合物6-羟基多巴胺（6-OH-DA）和6-氨基多巴胺（6-A-DA）进行的体外研究表明，去甲肾上腺素（NA）显著抑制6-OH-DA的自氧化，但不抑制6-A-DA的自氧化。对大鼠虹膜中肾上腺素能神经的体内研究表明，在用α-甲基-p-酪氨酸甲酯（H44/68）耗尽NA后，6-OH-DA的神经毒性效力增加，而6-A-DA的神经毒性效力未增加。通过测量相关的3-H-NA摄取减少来评估神经毒性。眼内注射NA可抵消6-OH-DA在未处理和H44/68预处理大鼠中的退行性作用。眼内NA不干扰6-A-DA的神经毒性。此外，章鱼胺不影响6-OH-DA或6-A-DA的自氧化速率或神经毒性效力。用3-H-6-OH-DA进行的对照实验表明，神经元内NA水平对6-OH-DA的神经元内积累没有显著影响。体外自氧化结果与体内神经毒性数据之间的平行关系表明，6-OH-DA和6-A-DA的神经毒性效力与其自氧化速率密切相关。神经元内NA对6-OH-DA退行性作用的控制可能是通过NA与6-OH-DA自氧化过程中由氧形成的自由基反应来介导的。
