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SEROTONIN RECEPTORS AND CHLORIDE CHANNELS

SEROTONIN RECEPTORS AND CHLORIDE CHANNELS
血清素受体和氯离子通道
批准号:
2264767
负责人:
RICARDO MILEDI MILEDI
金额:
$34.28万
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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项目成果

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中文摘要
翻译
5-羟色胺及其受体是主要神经递质的一部分。 中枢和外周神经系统的通路。它是 因此,重要的是要了解更多关于5-羟色胺作用的受体和 他们经营的渠道。为此,一个多学科的 将研究5-羟色胺受体的结构和功能,使用 青蛙卵母细胞和重组DNA的研究。这将提供信息 关于所有水平的神经递质受体和相关通道, 从他们的基因到他们的行动模式。 5-羟色胺受体将从大脑“移植”到 非洲爪哇卵母细胞通过从大鼠和人脑中分离信使RNA,以及 将其注射到卵母细胞中。翻译外源信使核糖核酸 卵母细胞使其获得功能性的5-羟色胺受体,它们是在那里制造的 比起在他们的天然脑细胞中,他们更易于研究。 此外,非洲爪哇卵母细胞是mRNAs极其灵敏的探测器。 编码神经递质受体和通道。因此,卵囊会 用于克隆参与细胞周期调控的受体和通道的基因 5-羟色胺对脑细胞的作用。这将通过一种新的方法来实现,即 避免了必须首先提纯蛋白质的困难任务。 5-羟色胺受体,从大脑移植到卵母细胞膜, 调解至少三种不同类型的响应;可能涉及 不同的受体。其中两种5-羟色胺反应是由 不同类型的氯离子通道,而另一种是由闭合引起的 K+通道。电生理、生化和免疫学 技术将被用来研究5-羟色胺受体和相关的通道, 以及细胞内受体-通道耦合系统,由 5HT。 除了被5-羟色胺激活的氯离子通道外,还有一个不同的氯离子通道 在卵母细胞中通过鱼雷电细胞的mRNA表达。这个信使核糖核酸将是 用于克隆电细胞通道,获得的克隆将被 用于克隆脑细胞的其他氯离子通道。氯离子通道是一种 中枢和外周神经元中非常重要的元素以及 肌肉、分泌和上皮细胞。因此,5-羟色胺受体和 CL-通道与多种人类疾病有关;例如, 精神抑郁、精神分裂症、唐氏综合症、库欣、亨廷顿 以及阿尔茨海默病、肌强直和囊性纤维化。因此,这 该研究旨在克隆5-羟色胺受体和氯离子通道,以研究它们的 结构和功能,因为结果无疑将有助于 了解并减轻一些人类疾病。
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