STRUCTURE AND FUNCTION OF SEROTONIN RECEPTORS

5-羟色胺（5-HT）及其受体是一种主要的神经递质 系统，其故障与各种人类疾病有关。 到 了解故障，并可能减轻其后果，我们 需要了解更多关于5-HT作用的受体。 为此目的 一个多学科的研究将作出的综合，结构和 用青蛙卵母细胞和重组DNA研究5-HT受体的功能 research. 5 HT受体将从大脑“移植”到大脑中。 从大鼠和人的卵母细胞中分离信使RNA 大脑，并将其注入卵母细胞。 外源mRNA的翻译 使其获得功能性的5 HT受体。 电生理技术将被用来研究离子膜 通道打开，或关闭，由5 HT的行动和参与循环 核苷酸、磷酸肌醇和钙离子作为通道操作者， 用生物化学和电生理学方法进行研究。 血清素 受体类型将通过药理学研究表征， 并会寻找有选择性的药物。 这些信息将帮助 开发可用于治疗5 HT病症的化合物， 系统 大脑mRNA将成为几项研究的主题。 比如说 受体和通道表达的mRNA从正常和患病的人 大脑将被调查是否与疾病有关， 如阿尔茨海默氏症、库欣和亨廷顿;以及 将通过从发育中的大脑中分离mRNA来研究5 HT受体。 并在卵母细胞中表达。 确定5 HT受体的结构 将使用两种方法：受体和基因的纯化 克隆。 单克隆抗受体抗体的生产和 合成寡核苷酸探针将大大有助于克隆基因。 然而，受体/通道克隆工作甚至将在这些之前开始。 制作。 将mRNA制备物分级分离以分离编码 for different不同receptor受体and channel通道. 部分纯化的mRNA 编码5 HT受体和氯离子通道的组分将用于 构建将通过各种程序筛选的cDNA文库， 包括卵母细胞中的功能测定。

Serotonin (5HT) and its receptors are part of a major neurotransmitter system, whose malfunction is implicated in a variety of human diseases. To understand the malfunction, and possibly alleviate its consequences, we need to know more about the receptors on which 5HT acts. For this purpose a multidisciplinary study will be made of the synthesis, structure and function of 5HT receptors, using frog oocytes and recombinant DNA research. 5HT receptors will 'transplanted' from the brain into the membrane of Xenopus oocytes by isolating messenger RNA, from rat and human brains, and injecting it into the oocytes. Translation of the foreign mRNA by the oocyte causes it to acquire functional 5HT receptors. Electrophysiological techniques will be used to study the ionic membrane channels opened, or closed, by 5HT action and the involvement of cyclic nucleotides, phosphoinostides and calcium ions as channel operators will be investigated with biochemical and electrophysiological methods. Serotonin receptor types will be characterized through pharmacological studies, and a search will be made for selective drugs. This information will help develop compounds that may be used in the treatment of disorders of the 5HT system. Brain mRNA will be the subject of several studies. For example, the receptors and channels expressed by mRNA from the normal and diseased human brain will be investigated for their possible involvement in diseases such as Alzheimer, Cushing and Huntington; and the ontogenetic development of 5HT receptors will be studied by isolating mRNA from the developing brains and expressing it in oocytes. To determine the structure of 5HT receptors two approaches will be used: purification of the receptors and gene cloning. Production of monoclonal anti-receptor antibodies and of synthetic oligonucleotide probes will help greatly in cloning the genes. However, the receptor/channel cloning work will start even before these are produced. mRNA preparations will be fractionated to separate mRNAs coding for different receptors and channels. The partially purified mRNA fractions coding for 5HT receptors and chloride channels will be used to construct cDNA libraries that will be screened by various procedures, including functional assays in oocytes.