IN VITRO SCREEN FOR A TYPICAL BETA-ADRENERGIC AGONISTS

描述(改编自申请人的摘要)：本报告的最终目标 研究是开发一种基于识别的肥胖症的疗法 新的β-肾上腺素能激动剂是一种选择性刺激 人类的生热作用。非典型(非β-1、β2)β-肾上腺素能 受体(β-AR)被认为是交感神经系统的媒介。 生热的刺激作用。非典型的β-激动剂已被证明 在动物模型中刺激产热并促进体重减轻 人体临床试验，但尽管它们具有相对的选择性，但相互作用 用β-1-AR和β-2-AR会产生副作用。激动剂的研究进展 对生热作用的刺激选择性将导致有用的 治疗学。拟议的研究计划的具体目标是 建立选择性产热β-激动剂筛选体系。 在第一阶段，我们建议使用聚合酶链式反应(PCR)和 鉴定和分离非典型肺炎基因的分子克隆技术 β-AR在人体产热部位的组织中表达。 在第二阶段，非典型β-ars的基因将被引入 中国仓鼠卵巢(CHO)细胞建立基质细胞系 表达功能性非典型受体，将用于筛选 潜在的致热激动剂。

DESCRIPTION (Adapted from applicant's abstract): The ultimate goal of this research is to develop a therapy for obesity based upon the identification of novel beta-adrenergic agonists which are selective stimulators of thermogenesis in humans. Atypical (non-beta-1, beta-2) beta-adrenergic receptors (beta-ARs) are thought to mediate sympathetic nervous system stimulation of thermogenesis. Atypical beta-agonists have been shown to stimulate thermogenesis and promote weight loss in animal models and in human clinical trials, but despite their relative selectivity, interactions with beta-1-AR and beta-2-AR produce side effects. Improvements in agonist selectivity for stimulation of thermogenesis would lead to useful therapeutics. The specific aim of the proposed research plan is to establish a screening system for selective thermogenic beta-agonists. During Phase I we propose to employ polymerase chain reaction (PCR) and molecular cloning techniques to identify and isolate genes for atypical beta-ARs expressed in tissues which are sites for thermogenesis in humans. During Phase II, the genes for atypical beta-ARs will be introduced into Chinese hamster ovary (CHO) cells to establish a matrix of cell lines expressing functional atypical receptors, which will them be used to screen potential thermogenic agonists.