REGULATION OF SEROTONIN-1 RECEPTORS

5-羟色胺（5-HT）是中枢神经系统中重要的神经递质 系统，并被认为涉及各种精神障碍。的 最近5 HT受体亚型的增殖提供了一个独特的机会， 研究这些亚型与精神障碍的关系， 开发亚型特异性药物来治疗这些疾病。的 本申请的长期目标是了解 不同的5-HT受体亚型在两个水平上。一是监管 在细胞膜受体蛋白水平上， 腺苷酸环化酶;第二个是基因调控， 受体的表达。我们建议使用5 HT（1B）受体， OK细胞系作为研究中枢神经系统5 HT（1）受体的模型系统。 HHT（1B）受体的下调和脱敏 OK细胞系将通过多种测定进行研究， 放射性配体结合和环AMP产生测定。我们建议克隆 来自OK细胞的5 HT（1B）受体和来自 老鼠的大脑这些克隆将被用作拟议研究的工具， 受体系统的调节。我们还计划确定 大鼠脑内5-HT（1）受体的分布和表达水平 通过北方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.