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用抗苯二氮䓬类单克隆抗体在哺乳动物大脑中证明苯二氮䓬类分子的存在。

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

作者信息

Sangameswaran L, de Blas A L

出版信息

Proc Natl Acad Sci U S A. 1985 Aug;82(16):5560-4. doi: 10.1073/pnas.82.16.5560.

DOI:10.1073/pnas.82.16.5560
PMID:2991934
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC391162/
Abstract

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.

摘要

一种抗苯二氮䓬单克隆抗体已被用于证明大脑中存在苯二氮䓬样分子。免疫细胞化学实验表明,这些分子是神经元性的而非神经胶质细胞性的,并且它们在整个大脑中广泛分布。免疫印迹显示几种脑肽中存在苯二氮䓬样表位。通过免疫亲和色谱从脑可溶性部分分离出小的苯二氮䓬样分子。它们阻断激动剂、反向激动剂和拮抗剂与神经元型苯二氮䓬受体的结合。神经递质γ-氨基丁酸增加苯二氮䓬受体对纯化的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䓬受体激动剂。然而,纯化的分子并不抑制氚标记的Ro 5-4864与“外周型”苯二氮䓬受体的结合。结果证明大脑中存在与苯二氮䓬受体结合的苯二氮䓬样分子。这些分子与其他人报道的内源性苯二氮䓬受体配体不同。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/341d/391162/8f4c61529f3c/pnas00356-0333-g.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/341d/391162/cddff00060d4/pnas00356-0332-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/341d/391162/1a4c73fca34e/pnas00356-0332-c.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/341d/391162/d401c71f608b/pnas00356-0332-d.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/341d/391162/745cd1a42983/pnas00356-0332-e.jpg
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