Fagervall I, Ross S B
J Neurochem. 1986 Aug;47(2):569-76. doi: 10.1111/j.1471-4159.1986.tb04537.x.
The inhibition of the A and B forms of monoamine oxidase (MAO) inside and outside serotonergic, noradrenergic, and dopaminergic synaptosomes in homogenates of rat hypothalamus or striatum by clorgyline, a selective and irreversible MAO-A inhibitor, and selegiline, a selective and irreversible MAO-B inhibitor, was examined. Intrasynaptosomal deamination at low concentrations of the substrates [14C]5-hydroxytryptamine ([14C]5-HT; 0.1 microM), [14C]noradrenaline (0.25 microM), [14C]3,4-dihydroxyphenylethylamine ([14C]dopamine; 0.25 microM), and [14C]tyramine (0.25 microM) was hindered by selective uptake inhibitors (citalopram, maprotiline, and amfonelic acid) in the incubation media. Thus, the difference between the deamination of 14C-amine in the absence and presence of the appropriate selective uptake inhibitor provided a measure of deamination in the specific aminergic synaptosomes. This was verified by determining the loss of MAO activity within noradrenergic and serotonergic systems after degeneration of the nerve terminals by the neurotoxins N-chloroethyl-N-ethyl-2-bromobenzylamine and p-chloroamphetamine. Results with the two inhibitors revealed that the A and B forms were responsible for 80 and 20%, respectively, of the deamination of [14C]5-HT within serotonergic synaptosomes from the hypothalamus. The deamination of [14C]noradrenaline within the noradrenergic synaptosomes from the hypothalamus and that of [14C]dopamine and [14C]tyramine within the striatal dopaminergic synaptosomes were due to MAO-A. About 10% of the deamination of [14C]noradrenaline, [14C]dopamine, and [14C]tyramine outside the noradrenergic or dopaminergic synaptosomes was brought about by the B form, with the remainder being deaminated by MAO-A.
研究了选择性不可逆单胺氧化酶A抑制剂氯吉兰和选择性不可逆单胺氧化酶B抑制剂司来吉兰对大鼠下丘脑或纹状体匀浆中血清素能、去甲肾上腺素能和多巴胺能突触体内部和外部单胺氧化酶(MAO)的A和B形式的抑制作用。在孵育介质中,选择性摄取抑制剂(西酞普兰、马普替林和安非他明)可阻碍低浓度底物[14C]5-羟色胺([14C]5-HT;0.1微摩尔)、[14C]去甲肾上腺素(0.25微摩尔)、[14C]3,4-二羟基苯乙胺([14C]多巴胺;0.25微摩尔)和[14C]酪胺(0.25微摩尔)的突触体内脱氨作用。因此,在不存在和存在适当的选择性摄取抑制剂的情况下,14C-胺脱氨作用的差异提供了特定胺能突触体中脱氨作用的一种度量。通过测定神经毒素N-氯乙基-N-乙基-2-溴苄胺和对氯苯丙胺使神经末梢变性后,去甲肾上腺素能和血清素能系统内MAO活性的丧失,对此进行了验证。两种抑制剂的结果显示,在下丘脑血清素能突触体中,A和B形式分别占[14C]5-HT脱氨作用的80%和20%。下丘脑去甲肾上腺素能突触体中[14C]去甲肾上腺素的脱氨作用以及纹状体多巴胺能突触体中[14C]多巴胺和[14C]酪胺的脱氨作用均归因于MAO-A。在去甲肾上腺素能或多巴胺能突触体外部,[14C]去甲肾上腺素、[14C]多巴胺和[14C]酪胺约10%的脱氨作用由B形式引起,其余由MAO-A脱氨。