Specific high-affinity saturable binding of [3H] R05-4864 to benzodiazepine binding sites in the rat cerebral cortex.
Specific high-affinity saturable binding of [3H] R05-4864 to benzodiazepine binding sites in the rat cerebral cortex.
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[3H] R05-4864 与大鼠大脑皮层中苯二氮卓结合位点的特异性高亲和力可饱和结合。
DOI：
10.1016/0014-2999(81)90405-2
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发表时间：
1981
影响因子：
5
通讯作者：
Yamamura,HI
中科院分区：
文献类型：
--
作者：
Schoemaker,H;Bliss,M;Yamamura,HI
苯二氮卓类药物与哺乳动物脑中的阿片相关受体以高亲和力结合。初步研究表明，存在单一同质群体的苯二氮卓类受体位点。然而，最近的研究提供了在大鼠脑中存在多种苯二氮卓受体的证据（Klepner等人，1979年）。苯并二氮杂还以高亲和力结合多种外周组织的膜，包括肾（Braestrup和Squires，1977; Regan等人，1981年）。这些组织中存在的苯二氮卓类受体与大脑中[3 H]-氟硝西泮标记的受体不同。例如，氯硝西泮是[3 H]-氟硝西泮与脑细胞膜结合的有效抑制剂，但在从肾细胞膜置换[3 H]-氟硝西泮方面几乎没有活性。另一方面，苯并二氮杂卓Ro 5 -4864，一种在大多数动物试验中缺乏抗焦虑样活性的临床活性抗焦虑药（Randall等人，1974），是肾结合位点的有效抑制剂，但在脑中未显示出显著活性。最近，具有高比活度的放射性标记的Ro 5 -4864已经可用。正如预期的那样，[3 H]-Ro 5 -4864以高亲和力（KD= 1.6 nM;手稿在制备中）与大鼠肾脏的膜制备物结合，可被纳摩尔浓度的地西泮和氟硝西泮置换。我们现在报告说
Benzodiazepines bind with high affinity to pharmacologically relevant receptors in the mammalian brain. Initial studies indicated the presence of a single homogeneous population of benzodiazepine receptor sites. However, more recent studies have provided evidence for the existence of multiple benzodiazepine receptors in the rat brain (Klepner et al., 1979). Benzodiazepines also bind with high affinity to membranes of a variety of peripheral tissues, including the kidney (Braestrup and Squires, 1977; Regan et al., 1981). The benzodiazepine receptor present in these tissues differs from that labelled by [3H]-flunitrazepam in the brain. For example, clonazepam is a potent inhibitor of [3H]-flunitrazepam binding to brain membranes, but is virtually inactive in displacing [3H]-flunitrazepam from kidney membranes. On the other hand, the benzodiazepine Ro5-4864, a clinically active anxiolytic devoid of anxiolytic-like activity in most animal tests (Randall et al., 1974), is a potent inhibitor of the kidney binding sites but fails to show significant activity in the brain. Recently, radiolabelled Ro5-4864 with high specific activity has become available. As expected,[3H]-Ro5-4864 binds with high affinity (KD= 1.6 nM; manuscript in preparation) to membrane preparations of the rat kidney, from which it can be displaced by nanomolar concentrations of diazepam and flunitrazepam. We now report