BIOLOGICAL AND BIOCHEMICAL CHARACTERIZATION OF SIGMA RECEPTORS

这个项目描述了生化、化学和药理学。 Sigma受体和配体的性质。在高浓度下， (Tris)羟甲基(氨甲烷)盐酸盐(Tris)抑制Sigma结合 受体以剂量依赖和竞争的方式。这一观察结果 提示Sigma介导的某些药物反应 受体可以被Tris掩盖。脑匀浆结合试验 揭示Sigma-1和Sigma-2受体亚型表现出不同 个体发育模式。Sigma-1受体相对保持不变 出生前至出生后(-3至90天)。Sigma-2受体密度 在出生前3天是第30天的10倍 Sigma-2和Sigma-1受体的密度相似。亚细胞 Sigma-1和Sigma-2受体的分布没有不同。不是 当比较时发现Sigma-1或Sigma-2受体的差异 遗传性营养不良的大鼠和它们的正常产仔。已溶解 大鼠肝脏中的Sigma受体可被分解成两个组分 电荷分配层析。饱和度分析显示类似 放射性标记的d-N-烯丙基去甲氧基甲氧基异丙唑碱与两个组分的亲和力， 提示它们不代表Sigma-1和Sigma-2受体。 对受体的进一步纯化正在进行中。

This project delineates biochemical, chemical, and pharmacological properties of sigma receptors and ligands. At high concentrations, (Tris)hydroxymethyl (aminomethane) Hcl (Tris) inhibits binding to sigma receptors in a dose-dependent and competitive manner. This observation suggests that certain pharmacological responses mediated by sigma receptors could be masked by Tris. Brain homogenate binding assays reveal that sigma-1 and sigma-2 receptor subtypes exhibit different ontogenetic patterns. Sigma-1 receptors remain relatively unchanged from prenatal to postnatal ages (-3 to 90 days). Sigma-2 receptor densities are 10-fold higher at 3 days before birth than at day 30 at which time the densities of sigma-2 and sigma-1 receptors are similar. Subcellular distributions of sigma-1 and sigma-2 receptors do not differ. No differences in sigma-1 or sigma-2 receptors are found when comparing genetically dystonic rats with their normal littermates. Solubilized sigma receptors from rat liver can be resolved into two components by charge partition chromatography. Saturation analysis reveals similar affinities for radiolabeled d-N-allylnormetazocine to both components, suggesting that they do not represent sigma-1 and sigma-2 receptors. Further purification of the receptors is underway.