Purification of a benzodiazepine from bovine brain and detection of benzodiazepine-like immunoreactivity in human brain.
Purification of a benzodiazepine from bovine brain and detection of benzodiazepine-like immunoreactivity in human brain.
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从牛脑中纯化苯二氮卓类药物并检测人脑中苯二氮卓类免疫反应性。
DOI：
10.1073/pnas.83.23.9236
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发表时间：
1986
影响因子：
11.1
通讯作者：
DeBlas,AL
中科院分区：
文献类型：
--
作者：
Sangameswaran,L;Fales,HM;Friedrich,P;DeBlas,AL
大鼠和牛脑中均存在一种内源性脑物质，可与具有激动剂特性的中枢型苯二氮卓类受体结合。该物质已通过免疫亲和色谱法从牛脑中纯化至均一，采用固定化单克隆抗苯二氮卓类抗体，然后采用Sephadex G-25凝胶过滤和两个反相HPLC步骤。纯化物质表征为苯二氮卓类N-去甲基地西泮（去甲地西泮）。用于鉴定的技术有质谱法、HPLC法、分光光度法、苯二氮卓受体结合法和免疫学技术。在所有测试的人脑中也发现了苯二氮卓类免疫反应性，包括自1940年以来储存在石蜡中的六个大脑，在苯二氮卓类药物首次合成之前15年。这些结果表明，天然来源的苯二氮卓类分子-可能还有苯二氮卓本身-存在于人类和其他哺乳动物的大脑中。
An endogenous brain substance that binds to the central-type benzodiazepine receptors with agonist properties is present in both rat and bovine brains. This substance has been purified to homogeneity from bovine brain by immunoaffinity chromatography on immobilized monoclonal anti-benzodiazepine antibody followed by gel filtration on Sephadex G-25 and two reversed-phase HPLC steps. The purified substance was characterized as the benzodiazepine N-desmethyldiazepam (nordiazepam). The techniques used for the identification were mass spectrometry, HPLC, spectrophotometry, benzodiazepine receptor binding, and immunological techniques. Benzodiazepine-like immunoreactivity was also found in all the human brains tested, including six brains that had been stored in paraffin since 1940, fifteen years before the first synthesis of benzodiazepines. These results show that benzodiazepine-like molecules of natural origin--and possibly benzodiazepines themselves--are present in human and other mammalian brains.