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[非单胺能神经元合成单胺:现实的错觉]

[Monoamine synthesis by non-monoaminergic neurons: illusion of reality].

作者信息

Ugriumov M V

出版信息

Ross Fiziol Zh Im I M Sechenova. 2009 Mar;95(3):273-82.

PMID:19449783
Abstract

Apart from monoaminergic neurons possessing the whole set of enzymes of monoamine synthesis from the precursor amino acid, the neurons expressing individual enzymes of monoamine synthesis have been discovered in the mid-eighties. Most numerous monoenzymatic neurons express individual enzymes of dopamine (DA), thyrosine hydroxylase (TH) or aromatic L-amino acid decarboxylase (AADC). Functional characteristics and the functional significance of the monoenzymatic neurons have been evaluated in a series of our studies, mainly of the hypothalamic arcuate nucleus (AN), one of the most important DA-ergic centers of the brain. It has been demonstrated that the AN of rats contains numerous monoenzymatic neurons. Their portion among the neurons expressing enzymes of DA synthesis exceeded 99 % whereas it decreased continuously in postnatal period still reaching 50 % in adulthood. It was shown that the monoenzymatic neurons expressing complementary enzymes of DNA synthesis produce this neurotransmitter in cooperation. In this case, L-tyrosine is transformed to L-DOPA in TH containing neurons that is followed by L-DOPA release and uptake to AADC containing neurons with a semi-specific membrane transporter of large neutral amino acids for DA synthesis. Turning on the expression of enzymes of DA synthesis in non-dopaminergic neurons is an adaptive reaction under the functional insufficiency of DA-ergic neurons. So, hyperprolactinemia that is developed under the degeneration of DA-ergic neurons of the AN and the deficiency of DA, the prolactin-inhibiting neurohormone, was compensated in due time to increase in number of monoenzymatic neurons and the strengthening of cooperative synthesis of DA in the nucleus. The same compensatory cooperative synthesis if DA is supposed to be turned on under the degeneration of DA-ergic neurons of the nigrostriatal system that was manifested by appearance of the neurons expressing enzymes of DA synthesis in the deafferentiated striatum in rats. The expression of enzymes of DA synthesis in non-dopaminergic neurons is under the control by intercellular signals. e.g., catecholamines. Thus, numerous non-monoaminergic neurons in the brain expressing individual complementary enzymes of monoamine synthesis produce monoamines in cooperation that is a compensatory reaction to a functional insufficiency of monoaminergic neurons.

摘要

除了单胺能神经元拥有从前体氨基酸合成单胺的全套酶之外,在20世纪80年代中期还发现了表达单胺合成个别酶的神经元。数量最多的单酶神经元表达多巴胺(DA)、酪氨酸羟化酶(TH)或芳香族L-氨基酸脱羧酶(AADC)的个别酶。我们在一系列研究中评估了单酶神经元的功能特征和功能意义,主要是对下丘脑弓状核(AN)进行研究,它是大脑中最重要的多巴胺能中心之一。已经证明大鼠的AN含有大量单酶神经元。它们在表达DA合成酶的神经元中所占比例超过99%,而在出生后时期持续下降,成年时仍达到50%。结果表明,表达DNA合成互补酶的单酶神经元协同产生这种神经递质。在这种情况下,L-酪氨酸在含TH的神经元中转化为L-多巴,随后L-多巴释放并被含AADC的神经元摄取,通过大中性氨基酸的半特异性膜转运体用于DA合成。在多巴胺能神经元功能不足的情况下,非多巴胺能神经元中DA合成酶表达的开启是一种适应性反应。因此,在AN的多巴胺能神经元退化以及催乳素抑制神经激素DA缺乏的情况下出现的高催乳素血症,会随着单酶神经元数量的增加和核内DA协同合成的增强而适时得到补偿。如果黑质纹状体系统的多巴胺能神经元退化,预计同样的DA补偿性协同合成会开启,这在大鼠去传入纹状体中出现表达DA合成酶的神经元中得到体现。大脑中许多表达单胺合成个别互补酶的非单胺能神经元协同产生单胺,这是对单胺能神经元功能不足的一种补偿反应。

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