Sieghart W
J Neural Transm. 1985;63(3-4):191-208. doi: 10.1007/BF01252025.
Several lines of evidence from reversible binding studies seem to indicate there are at least two "central" benzodiazepine receptor subtypes, the BZ1 and BZ2 receptors. Irreversible binding studies, using 3H-flunitrazepam as a photoaffinity label for benzodiazepine receptors, not only are in perfect agreement with the data from reversible binding studies but extend these studies by identifying P51, a protein with apparent molecular weight 51,000, as a protein associated with the BZ1 receptor and by suggesting that the BZ2 receptor might actually consist of several different benzodiazepine receptors associated with different and distinct proteins irreversibly labeled by 3H-flunitrazepam. Other reversible binding studies have accumulated indicating the existence of several different conformations of benzodiazepine receptors. Irreversible binding studies support this conclusion and in addition suggest the existence of four different benzodiazepine binding sites within the GABA-benzodiazepine receptor complex. It is therefore hypothesized that there are several different GABA-benzodiazepine receptor subtypes all of which have four distinct benzodiazepine binding sites which can exist in at least three different but freely interconvertible conformations. This hypothesis can account for all experimental observations obtained so far and might partially explain the distinct clinical effects of structurally similar benzodiazepines.
来自可逆性结合研究的几条证据线索似乎表明，至少存在两种“中枢性”苯二氮䓬受体亚型，即BZ1和BZ2受体。使用3H-氟硝西泮作为苯二氮䓬受体的光亲和标记物的不可逆性结合研究，不仅与可逆性结合研究的数据完全一致，而且通过鉴定P51（一种表观分子量为51,000的蛋白质）为与BZ1受体相关的蛋白质，并提出BZ2受体可能实际上由几种不同的苯二氮䓬受体组成，这些受体与被3H-氟硝西泮不可逆标记的不同且独特的蛋白质相关联，从而扩展了这些研究。其他可逆性结合研究积累的数据表明存在几种不同构象的苯二氮䓬受体。不可逆性结合研究支持这一结论，此外还表明在GABA-苯二氮䓬受体复合物内存在四个不同的苯二氮䓬结合位点。因此，有人提出存在几种不同的GABA-苯二氮䓬受体亚型，所有这些亚型都有四个不同的苯二氮䓬结合位点，这些位点可以以至少三种不同但可自由相互转化的构象存在。这一假说可以解释迄今为止获得的所有实验观察结果，并且可能部分解释结构相似的苯二氮䓬类药物的不同临床效果。
