Computer-assisted analysis of dextromethorphan and (+)-3-(-3-hydroxyphenyl)-N-(1-propyl)piperidine binding sites in rat brain. Allosteric effects of ropizine.
Computer-assisted analysis of dextromethorphan and (+)-3-(-3-hydroxyphenyl)-N-(1-propyl)piperidine binding sites in rat brain. Allosteric effects of ropizine.
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大鼠脑中右美沙芬和 ( )-3-(-3-羟苯基)-N-(1-丙基)哌啶结合位点的计算机辅助分析。
DOI：
10.1016/0024-3205(90)90367-z
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发表时间：
1990
期刊：
影响因子：
6.1
通讯作者：
Musacchio,JM
中科院分区：
文献类型：
--
作者：
Klein,M;Musacchio,JM
对右美沙芬 (DM) 和 (+)-3-(3-羟基苯基)-N-(1-丙基)哌啶 ((+)-3-PPP) 之间的自位移和交叉位移研究的计算机辅助分析表明，在大鼠大脑中，每种配体存在两个高亲和力和一个低亲和力结合位点。常见的 DM1/σ1 位点是一个高亲和力位点，10 μM 罗哌嗪变构地使该位点的亲和力增加 4 至 5 倍。 DM 和 (+)-3-PPP 的 DM1/σ1 的 Kd 值分别为 17 和 11 nM。 DM 与第二个高亲和力位点 (R2) 结合，Kdof 为 15 nM；该位点对 (+)-3-PPP 的亲和力较低。相反，(+)-3-PPP 以高亲和力 (Kd53 nM) 与另一个对 DM 具有低亲和力的位点 (R3) 结合。大鼠中常见DM1/σ1位点的Bmax比豚鼠中的Bmax小约十倍。因此，从一个物种推断到另一个物种时应格外谨慎。由于 DM 和大多数 σ 配体结合多个位点，并非所有位点都是共享的，因此重要的是不要将这些配体的复杂药理作用归因于单一假设受体。
Computer-assisted analysis of self- and cross-displacement studies between dextromethorphan (DM) and (+)-3-(3-hydroxyphenyl)-N-(1-propyl) piperidine ((+)-3-PPP) demonstrated in the rat brain the existence of two high-affinity and one low-affinity binding site for each ligand. One high-affinity site is the common DM1/σ1site, the affinity of which is allosterically increased 4 to 5-fold by 10 μM ropizine. The Kdvalues of the DM1/σ1for DM and (+)-3-PPP are 17 and 11 nM respectively. DM binds to the second high-affinity site (R2) with a Kdof 15 nM; this site has low affinity for (+)-3-PPP. Conversely, (+)-3-PPP binds with high affinity (Kd53 nM) to another site (R3), that has low-affinity for DM. The Bmaxof the common DM1/σ1site in the rat is about ten times smaller than that in the guinea pig. Thus, extreme caution should be exercised in extrapolating from one species to another. Since DM and most σ ligands bind to more than one site, not all of which are shared, it is important not to attribute the complex pharmacological effects of these ligands to a single hypothetical receptor.