EVOLUTION OF NEUROTRANSMITTER RECEPTORS

神经递质受体的进化

• 批准号: 3945284
• 负责人: J C VENTER
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3945284
• 关键词: acetylcholinesterase; affinity chromatography; biochemical evolution; brain; gamma aminobutyrate; gel electrophoresis; genetic library; genetic mapping; heart; human tissue; isoelectric point; molecular cloning; molecular genetics; monoclonal antibody; species difference

The purpose of this project is to examine the structural and functional evolution of neurotransmitter receptor proteins. Using muscarinic cholinergic and beta adrenergic receptors as the initial model sysems we have isolated and characterized these receptors from the brains and hearts of a wide variety of species. Brain and heart tissue have been obtained from all vertebrate classes including mammals, birds, reptiles, amphibians, and fish as well as from lower species including insects (Drosophila). Data from muscarinic receptor studies demonstrate that out of all of the parameters studied (SDS gel molecular weight, isoelectric point, monoclonal antibody cross reactivity, agonist affinity, antagonist affinity, stereospecificity of ligand binding, GTP shifts of agonist affinity, and receptor density) only receptor density appears to have changed over 900 million years of evolution gradually increasing in higher species. Muscarinic receptors have been purified from human brain, rat brain and heart, pig heart and shark brain and heart in order to compare primary structures in detail. The evolutionary relationship between muscarinic cholinergic receptors and other neurotransmitter receptors is also being studied. Protein sequence data and defined gene probes are being employed to follow the evolution of adrenergic, cholinergic and GABAergic receptors. We have cloned and sequenced beta and muscarinic genes from human and rat and have isolated a number of clones from other species. In particular, a positive clone from Drosophila genomic library has been isolated. Partial sequence data reveals that this clone contains a stretch of fifty- four nucleotides which has 84 homology with the corresponding human beta2 sequence. When the sequence is translated into amino acids and favored substitutions are considered, the homology goes up to 100. Although the exact nature of this beta2-like gene is still unknown, it may provide valuable information toward our understanding of the evolution of neural receptors. *(Transferred from LNP on 7/87).

该项目的目的是检查结构和 神经递质受体蛋白的功能进化。 使用 毒蕈碱胆碱能和β肾上腺素能受体作为初始受体， 我们已经分离并表征了这些受体的模型系统 各种各样的物种的大脑和心脏。 大脑和 心脏组织已经从所有脊椎动物类中获得 包括哺乳动物、鸟类、爬行动物、两栖动物和鱼类， 来自低等物种，包括昆虫（果蝇）。 数据从 毒蕈碱受体研究表明，在所有的 研究的参数（SDS凝胶分子量，等电点， 单克隆抗体交叉反应性，激动剂亲和力，拮抗剂 亲和力、配体结合的立体特异性、激动剂的GTP移位 亲和力和受体密度），只有受体密度似乎 逐渐改变了9亿年的进化过程 更高的物种。 毒蕈碱受体已经被 从人脑、大鼠脑和心脏、猪心和 鲨鱼的大脑和心脏，以比较其初级结构 详细 毒蕈碱与 胆碱能受体和其他神经递质受体也是 被研究。 蛋白质序列数据和定义的基因探针是 被用来追踪肾上腺素能，胆碱能 和GABA能受体。 我们克隆并测序了β 和毒蕈碱基因，并已分离出一种 其他物种的克隆数量。 特别是，积极的 从果蝇基因组文库中分离到一个克隆。 部分 序列数据显示，该克隆包含一段50- 4个核苷酸，与相应的同源性为84 人类β 2序列。 当序列被翻译成 考虑氨基酸和有利的取代， 同源性上升到100。 虽然这件事的本质 β 2样基因仍然未知，它可能提供有价值的 对我们理解神经系统进化的信息 受体。 * （1987年7月从利比里亚国家警察调来）。