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STUDIES ON SEROTONIN RECEPTORS AND CHLORIDE CHANNELS

STUDIES ON SEROTONIN RECEPTORS AND CHLORIDE CHANNELS
血清素受体和氯离子通道的研究
批准号:
3406582
负责人:
RICARDO MILEDI MILEDI
金额:
$32.59万
依托单位国家:
美国
项目类别:
财政年份:
1986
资助国家:
美国
项目状态:
已结题
起止时间:
1986-03-01 至 1996-02-28

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中文摘要
翻译
5-羟色胺(5-HT)及其受体是主要的神经递质 中枢神经系统和外周神经系统的信号通路。 是 因此,重要的是要了解更多关于5 HT作用的受体, 他们经营的渠道。 为此,一个多学科 研究将作出的结构和功能的5 HT受体,使用 青蛙卵母细胞和重组DNA研究。 这将提供信息 关于神经递质受体和相关通道的所有水平, 从基因到行为模式 5-HT受体将从大脑“移植”到脑细胞膜上, 从大鼠和人脑中分离信使RNA, 注入卵母细胞。 外源mRNA的翻译 卵母细胞使其获得功能性5HT受体, 比在它们的原生脑细胞中更容易研究。 此外,非洲爪蟾卵母细胞是极其敏感的mRNA检测器 编码神经递质受体和通道。 因此,卵囊将 可用于克隆参与细胞凋亡的受体和通道的基因, 5-HT对脑细胞的作用。 这将通过一种新颖的方法来实现, 避免了必须首先纯化蛋白质的困难任务。 从大脑移植到卵母细胞膜的5-HT受体, 至少有三种不同类型的反应;可能涉及 不同的受体。 其中两种5HT反应是由开放的 不同类型的Cl-通道,而另一种是由关闭 K+通道 电生理、生化和免疫学 技术将用于研究5-HT受体和相关通道, 以及细胞内受体-通道偶联系统, 5 HT。 除了5HT激活的Cl-通道外, 在卵母细胞中通过来自电鳐电细胞的mRNA表达。 这种mRNA将 用于克隆电细胞通道,然后将获得的克隆 用于克隆脑细胞的其他氯离子通道。 氯离子通道是一种 在中枢和外周神经元以及 肌肉、分泌和上皮细胞。 因此,5HT受体和 Cl-通道与多种人类疾病有关;例如, 精神抑郁症、精神分裂症、唐氏综合症、库欣氏症、亨廷顿舞蹈症 以及阿尔茨海默病、肌强直和囊性纤维化。 因此本 本研究旨在克隆5HT受体和Cl-通道,以研究它们的作用机制。 结构和功能,因为结果无疑将有助于 了解和减轻人类的一些疾病。
英文摘要
Serotonin (5HT) and its receptors are part of major neurotransmitter pathways in both the central and peripheral nervous systems. It is therefore important to know more about the receptors on which 5HT acts and the channels which they operate. for this purpose a multidisciplinary study will be made of the structure and function of 5HT receptors, using frog oocytes and recombinant DNA research. This will provide information about the neurotransmitter receptors and associated channels at all levels, from their genes to their mode of action. 5HT receptors will be '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, where they are made more amenable to study than if they were in their native brain cells. Furthermore, Xenopus oocytes are extremely sensitive detectors of mRNAs coding for neurotransmitter receptors and channels. Therefore, oocyst will be used for cloning the genes of the receptors and channels involved in the action of 5HT on brain cells. This will be done by a novel approach that avoids the difficult task of having first to purify the proteins. 5HT receptors, transplanted from the brain into the oocyte membrane, mediate at least three different types of responses; possibly involving different receptors. Two of the 5HT responses are caused by the opening of different types of Cl- channels, while the other is caused by the closing of K+-channels. Electrophysiological, biochemical and immunological techniques will be used to study the 5HT receptors and associated channels, as well as the intracellular receptor-channel coupling systems operated by 5HT. Apart from the Cl- channels activated by 5HT, a different Cl- channel is expressed in oocytes by mRNA from Torpedo electrocytes. This mRNA will be used to clone the electrocyte channel, and the clones obtained will then be used to clone other Cl- channels of brain cells. Chloride channels are a very important element in central and peripheral neurons as well as in muscle, secretory and epithelial cells. Accordingly 5HT receptors and Cl-channels have been implicated in a wide variety of human diseases; e.g., mental depression, schizophrenia, Down's syndrome, Cushing's, Huntington and Alzheimer diseases, myotonia and cystic fibrosis. Therefore, this study aims at cloning 5HT receptors and Cl- channels to study their structure and function because the results will undoubtedly help to understand and alleviate some human diseases.
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A NOVEL CLASS OF MAMMALIAN GABA RECEPTOR
  • 批准号:
    2248111
  • 项目类别:
  • 资助金额:
    $16.32万
  • 财政年份:
    1991
  • 负责人:
    RICARDO MILEDI MILEDI
  • 依托单位:
A NOVEL CLASS OF MAMMALIAN GABA RECEPTOR
  • 批准号:
    3387902
  • 项目类别:
  • 资助金额:
    $17.97万
  • 财政年份:
    1991
  • 负责人:
    RICARDO MILEDI MILEDI
  • 依托单位:
A NOVEL CLASS OF MAMMALIAN GABA RECEPTOR
  • 批准号:
    3387904
  • 项目类别:
  • 资助金额:
    $15.69万
  • 财政年份:
    1991
  • 负责人:
    RICARDO MILEDI MILEDI
  • 依托单位:
STRUCTURE AND FUNCTION OF SEROTONIN RECEPTORS
  • 批准号:
    3406579
  • 项目类别:
  • 资助金额:
    $28.4万
  • 财政年份:
    1986
  • 负责人:
    RICARDO MILEDI MILEDI
  • 依托单位:
海外基金