Nielsen M, Braestrup C
Nature. 1980 Aug 7;286(5773):606-7. doi: 10.1038/286606a0.
High-affinity binding of 3H-diazepam and 3H-flunitrazepam has provided evidence for the presence of benzodiazepine receptors on brain neurones. Pharmacological evidence showing a clear correlation between receptor affinity and in vivo pharmacological potency for several benzodiazepines and a link between benzodiazepine receptors and GABA (gamma-amino-butyric acid) receptors at the molecular level, indicates that these receptors are relevant to the pharmacological and clinical effects of benzodiazepines. In searching for possible endogeneous ligands for benzodiazepine receptors we have recently isolated ethyl beta-carboline-3-carboxylate (beta-CCE) found human urine and brain, and shown that beta-CCE has a higher affinity than diazepam for brain benzodiazepine receptors. beta-CCE itself is probably not present in the brain, but may be closely related to an endogenous benzodiazepine receptor ligand. We report here that beta-CCE, in contrast to benzodiazepines, can distinguish clearly between benzodiazepine receptors in cerebellum and hippocampus. This result strongly indicates that benzodiazepine receptors are not a single class of non-interacting entities. It has not been possible to determine whether two distinct receptors are present and/or whether true negative cooperativity exists among hippocampal, but not cerebellar, benzodiazepine receptors.
3H-地西泮和3H-氟硝西泮的高亲和力结合为脑神经元上存在苯二氮䓬受体提供了证据。药理学证据表明，几种苯二氮䓬类药物的受体亲和力与体内药理活性之间存在明显相关性，且在分子水平上苯二氮䓬受体与GABA（γ-氨基丁酸）受体之间存在联系，这表明这些受体与苯二氮䓬类药物的药理和临床作用相关。在寻找苯二氮䓬受体可能的内源性配体时，我们最近从人尿和脑中分离出了β-咔啉-3-羧酸乙酯（β-CCE），并表明β-CCE对脑苯二氮䓬受体的亲和力高于地西泮。β-CCE本身可能不存在于脑中，但可能与一种内源性苯二氮䓬受体配体密切相关。我们在此报告，与苯二氮䓬类药物不同，β-CCE能够清楚地区分小脑和海马体中的苯二氮䓬受体。这一结果有力地表明，苯二氮䓬受体不是单一类别的非相互作用实体。目前还无法确定海马体（而非小脑）中的苯二氮䓬受体是否存在两种不同的受体和/或是否存在真正的负协同作用。
