REGULATION OF SEROTONIN-1 RECEPTORS

5-羟色胺是中枢神经系统中一种重要的神经递质。 并被认为与各种精神障碍有关。这个 最近5-羟色胺受体亚型的增殖提供了一个独特的机会 研究这些亚型在精神障碍中的作用 开发针对亚型的药物来治疗这些疾病。这个 本应用程序的长期目标是了解 不同的5-羟色胺受体亚型在两个水平上。第一个是监管。 膜上受体蛋白的水平及其相互关系 去腺化环化酶；第二个是基因调控 受体的表达。我们建议使用5-羟色胺(1B)受体 OK细胞系作为研究中枢5-羟色胺(1)受体的模型系统。 5-羟色胺(1B)受体同源下调和脱敏 OK细胞系将通过各种检测方法进行研究，包括 放射配基结合和环化AMP产物分析。我们打算克隆 来自OK细胞的5HT(1B)受体和来自OK细胞的1B和/或1D受体 老鼠的大脑。这些克隆将被用作拟议的研究的工具 受体系统的调节。我们还计划定义组织 5-羟色胺(1)受体在大鼠脑内的分布和表达水平 经Northern印迹分析和原位杂交。

Serotonin (5HT) is an important neurotransmitter in the central nervous system and is thought to be involved in a variety of mental disorders. The recent proliferation of 5HT receptor subtypes provides a unique opportunity to study the involvement of these subtypes in mental disorders and to develop subtype-specific drugs for the treatment of these disorders. The long-term objective of this application is to understand the regulation of the various 5HT, receptor subtypes on two levels. The first is regulation at the level of the receptor protein in the membrane and its relationship to adenylate cyclase; the second is the genetic regulation of the expression of the receptor. We propose to use the 5HT(1B) receptor in the OK cell line as a model system to study the 5HT(1) receptors in the CNS. Homologous down-regulation and desensitization of the 5HT(1B) receptor in the OK cell line will be studied by a variety of assays including radioligand binding and cyclic AMP production assays. We propose to clone the 5HT(1B) receptor from the OK cell and the 1B and/or 1D receptor from rat brain. These clones will be used as tools in the proposed studies of the regulation of the receptor system. We also plan to define the tissue distribution and level of expression of 5HT(1) receptors in the rat brain by Northern blot analysis and in situ hybridization.