Sigma Receptor Binding Assays.
Sigma Receptor Binding Assays.
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DOI：
10.1002/0471141755.ph0134s71
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发表时间：
2015-12-08
影响因子：
--
通讯作者：
Ruoho AE
中科院分区：
文献类型：
--
作者：
Chu UB;Ruoho AE
Sigma受体是一类小分子调节的、主要与内质网(ER)膜相关的受体，分为两类：Sigma-1受体(S1R)和Sigma-2受体(S2R)。S1R和S2R都与一些药物结合，包括抗精神病药物、氟哌啶醇和阿片类止痛剂(+)-五唑碱。Sigma受体与神经系统相关的多种疾病病理有关，包括影响运动控制的疾病，如肌萎缩侧索硬化症(ALS)和Alzeimher病。本单元介绍了使用放射性配基结合分析对S1R和S2R进行药理学表征的方法。在第一部分中，我们用放射性配基饱和结合分析来确定S1R的受体密度，并用竞争抑制法来表征新化合物与S1R的亲和力，方法是使用选择性的S1R配体[~3H]-(+)-五唑辛。第二部分介绍了非选择性S1R和S2R配体[~3H]-1，3-二(2-甲苯基)胍([~3H]-DTG)与S2R的放射配基饱和结合分析和竞争抑制分析。
Sigma receptors belong to a class of small molecule-regulated, primarily endoplasmic reticulum (ER) membrane-associated receptors, of which there are two subtypes: the Sigma-1 receptor (S1R) and the Sigma-2 receptor (S2R). Both S1R and S2R bind to a number of drugs including antipsychotic, haloperidol, and the opioid analgesic, (+)-pentazocine. Sigma receptors are implicated in multiple disease pathologies associated with the nervous system including diseases affecting motor control such as Amyotrophic Lateral Sclerosis (ALS) and Alzeimher's disease. This unit describes methods for the pharmacological characterization of S1R and S2R using radioligand-binding assays. In the first section, radioligand saturation binding assay to determine receptor densities and competitive inhibition assays to characterize affinities of novel compounds are presented for S1R using the selective S1R ligand, [3H]-(+)-pentazocine. The second section describes radioligand saturation binding assay and competitive inhibition assays for the S2R using a non-selective S1R and S2R ligand, [3H]-1,3-di(2-tolyl)guanidine ([3H]-DTG).