Phenytoin differentially modulates the affinity of agonist and antagonist ligands for σ1 receptors of guinea pig brain
Phenytoin differentially modulates the affinity of agonist and antagonist ligands for σ1 receptors of guinea pig brain
复制标题
DOI：
10.1002/syn.20103
复制
发表时间：
2005-03-01
期刊：
影响因子：
2.3
通讯作者：
Del Pow, E
中科院分区：
文献类型：
--
作者：
Cobos, EJ;Baeyens, JM;Del Pow, E
我们评估了苯妥英 (DPH) 对豚鼠脑中激动剂或拮抗剂 sigma(1) 配体的 sigma-1 (sigma(1)) 受体亲和力的影响。异源竞争实验表明，DPH（250 muM 和 1 mM）浓度依赖性地增加了 sigma1 激动剂右美沙芬、(+)-SKF-10,047、(+)-3-PPP 和 PRE-084 的亲和力。然而，DPH 250 muM 和 1 mM 均不会增加（事实上，它们略微降低）sigma(1) 受体拮抗剂氟哌啶醇、BD 1063、NE-100、黄体酮和 BD 1047 的亲和力。这些发现表明，DPH 对 sigma(1) 受体配体亲和力的变构调节取决于配体的激动剂或拮抗剂特征。因此，体外确定 DPH 对 sigma(1) 配体亲和力的差异调节似乎构成了一个可以预测不同 sigma(1) 配体药理学特征的程序。 (C) 2005 Wiley-Liss, Inc.
We evaluated the effects of phenytoin (DPH) on the affinity for sigma-1 (sigma(1)) receptors of agonist or antagonist sigma(1) ligands in guinea pig brain. Heterologous competition experiments showed that DPH (250 muM and 1 mM) concentration-dependently increased the affinity of the sigma1 agonists dextromethorphan, (+)-SKF-10,047, (+)-3-PPP, and PRE-084. However, neither DPH 250 muM nor 1 mM increased (in fact, they slightly decreased) the affinity of the sigma(1) receptor antagonists haloperidol, BD 1063, NE-100, progesterone, and BD 1047. These findings suggest that allosteric modulation by DPH of the affinity of sigma(1) receptor ligands depends on the agonist or antagonist characteristics of the ligand. Therefore, determining in vitro the differential modulation by DPH of sigma(1) ligand affinity appears to constitute a procedure that can predict the pharmacological profile of different sigma(1) ligands. (C) 2005 Wiley-Liss, Inc.