Demonstration of benzodiazepine-like molecules in the mammalian brain with a monoclonal antibody to benzodiazepines.

Demonstration of benzodiazepine-like molecules in the mammalian brain with a monoclonal antibody to benzodiazepines.
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使用苯二氮卓类单克隆抗体在哺乳动物大脑中展示苯二氮卓类分子。

DOI:
10.1073/pnas.82.16.5560
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发表时间:
1985
影响因子:
11.1
通讯作者:
deBlas,AL
deBlas,AL
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Sangameswaran,L;deBlas,AL

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抗苯二氮卓类单克隆抗体已被用于证明脑中存在苯二氮卓类分子。免疫细胞化学实验表明,这些分子是神经元,而不是神经胶质细胞,它们普遍分布在整个大脑。免疫印迹表明在几种脑肽中存在苯二氮卓类表位。通过免疫亲和层析从脑可溶性部分中分离出苯二氮卓类小分子。它们阻断激动剂、反向激动剂和拮抗剂与神经元型苯二氮卓受体的结合。神经递质γ-氨基丁酸增加苯二氮卓受体对纯化内源性分子的亲和力。结果表明,免疫亲和纯化的分子表现得像神经元型苯二氮卓受体激动剂。然而,纯化的分子不抑制氚化Ro 5-4864与“外周型”苯二氮卓受体的结合。结果表明,大脑中存在与苯二氮卓受体结合的苯二氮卓类分子。这些分子不同于其他人报道的内源性苯二氮卓受体配体。
An anti-benzodiazepine monoclonal antibody has been used to demonstrate the existence of benzodiazepine-like molecules in the brain. Immunocytochemical experiments show that these molecules are neuronal and not glial and that they are ubiquitously distributed throughout the brain. Immunoblots indicate the presence of benzodiazepine-like epitopes in several brain peptides. Small benzodiazepine-like molecules were isolated from the brain soluble fraction by immunoaffinity chromatography. They block the binding of agonists, inverse agonists, and antagonists to the neuronal-type benzodiazepine receptor. The neurotransmitter gamma-aminobutyric acid increases the affinity of the benzodiazepine receptor for the purified endogenous molecules. The results indicate that the immunoaffinity-purified molecules behave like the neuronal-type benzodiazepine receptor agonists. The purified molecules, however, do not inhibit the binding of tritiated Ro 5-4864 to the "peripheral-type" benzodiazepine receptor. The results demonstrate the existence of benzodiazepine-like molecules in the brain that bind to the benzodiazepine receptor. These molecules are different from the endogenous benzodiazepine receptor ligands reported by others.