BIOLOGICAL AND BIOCHEMICAL CHARACTERIZATION OF SIGMA RECEPTORS

Sigma 受体的生物学和生化特征

• 批准号: 3775024
• 负责人: T P SU
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON DRUG ABUSE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3775024
• 关键词: buffers; chromatography; dosage; drug receptors; laboratory rat; ligands; neuroanatomy; neuropharmacology; protein purification; protein structure function; radiotracer; receptor binding

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.

这个项目描绘了生物化学、化学和药理学 σ受体和配体的性质。 在高浓度下， （三）羟甲基（氨基甲烷）盐酸盐（Tris）抑制与σ的结合 受体以剂量依赖性和竞争性的方式。 该观察结果 表明由σ介导的某些药理学反应 受体可能被三羟甲基氨基甲烷所掩盖。 脑匀浆结合测定 揭示了sigma-1和sigma-2受体亚型表现出不同的 个体发育模式 σ-1受体相对保持不变， 产前至产后年龄（-3至90天）。 σ-2受体密度 出生前3天比出生后30天高10倍， σ-2和σ-1受体的密度相似。 亚细胞 σ-1和σ-2受体的分布没有不同。 没有 当比较时发现sigma-1或sigma-2受体的差异 遗传性肌张力障碍大鼠与正常同窝出生的大鼠。 溶解 来自大鼠肝脏的σ受体可以通过以下方式分解成两种组分： 电荷分配色谱法 饱和度分析显示类似 放射性标记的d-N-烯丙基去甲甲唑辛对两种组分的亲和力， 表明它们不代表σ-1和σ-2受体。 受体的进一步纯化正在进行中。