Cotzias G C, Tang L C, Ginos J Z
Proc Natl Acad Sci U S A. 1974 Jul;71(7):2715-9. doi: 10.1073/pnas.71.7.2715.
The brain uptake of amines that do not enter the brain or enter it poorly was promoted by noncompetitive inhibitors of monoamine oxidase, as shown by behavioral and chemical criteria. Mice pretreated with water or enzyme inhibitors other than those mentioned were placid after receiving dopamine (3,4-dihydroxyphenethylamine). Mice pretreated with monoamine oxidase inhibitors (nialamide or iproniazid) showed upon treatment with dopamine the brisk motor responses characteristic of treatment with its precursor, L-dopa (3,4-dihydroxyphenylalanine). After receiving dopamine, intact nialamide-pretreated mice showed marked increases of brain dopamine, in contrast to water-pretreated test mice or water-treated controls. In unilaterally caudectomized, nialamide-pretreated mice, dopamine induced marked lateral curving of the body toward the lesion followed by running in that direction. Noradrenaline or adrenaline induced curving in caudectomized mice, whereas intact ones remained placid.These catecholamines are bound and inactivated by monoamine oxidase. The cerebral uptakes of chemicals that are bound but not inactivated by monoamine oxidase were thereafter tested. Nialamide induced increased behavioral responses to apomorphine and to N-propyl noraporphine, increased cerebral concentrations of both, and a deep coloration of the brain from methylene blue (bound by monoamine oxidase) but not Evans blue (bound by albumin). Even large doses of nialamide, however, failed to affect the behavioral responses to oxotremorine, which has cholinergic rather than adrenergic or dopaminergic properties. Mitochondrial monoamine oxidase seems therefore to play a specific regulatory role in the transport of substances that it binds, either to inactivate or to release them.
行为学和化学标准显示，单胺氧化酶的非竞争性抑制剂可促进那些无法进入大脑或进入大脑能力较差的胺类物质的脑摄取。用除上述提及的酶抑制剂以外的水或酶抑制剂预处理的小鼠，在接受多巴胺（3,4 - 二羟基苯乙胺）后表现得很平静。用单胺氧化酶抑制剂（尼亚酰胺或异烟酰异丙肼）预处理的小鼠，在用多巴胺处理后，表现出其前体L - 多巴（3,4 - 二羟基苯丙氨酸）处理时特有的轻快运动反应。与用水预处理的试验小鼠或水处理的对照相比，完整的经尼亚酰胺预处理的小鼠在接受多巴胺后，脑内多巴胺显著增加。在单侧切除尾状核、经尼亚酰胺预处理的小鼠中，多巴胺会导致身体明显向损伤侧弯曲，随后朝该方向奔跑。去甲肾上腺素或肾上腺素会使切除尾状核的小鼠发生弯曲，而完整小鼠则保持平静。这些儿茶酚胺会被单胺氧化酶结合并失活。此后测试了那些被单胺氧化酶结合但未失活的化学物质的脑摄取情况。尼亚酰胺会增加对阿扑吗啡和N - 丙基去甲阿朴吗啡的行为反应，增加两者在脑内的浓度，并使亚甲蓝（被单胺氧化酶结合）导致脑颜色变深，但对伊文思蓝（被白蛋白结合）无此作用。然而，即使是大剂量的尼亚酰胺也未能影响对毒扁豆碱的行为反应，毒扁豆碱具有胆碱能而非肾上腺素能或多巴胺能特性。因此，线粒体单胺氧化酶似乎在其结合的物质的转运中发挥特定的调节作用，要么使其失活，要么将其释放。
