EVOLUTION OF NEUROTRANSMITTER RECEPTORS

本项目的目的是检查结构和 神经递质受体蛋白的功能进化。vbl.使用 以M胆碱能和β-肾上腺素能受体为起始受体 我们已经分离并鉴定了这些受体的模型系统 来自各种各样物种的大脑和心脏。大脑和 心脏组织已经从所有脊椎动物类别中获得 包括哺乳动物、鸟类、爬行动物、两栖动物和鱼类以及 来自低等物种，包括昆虫(果蝇)。数据来自 毒扁豆碱受体研究表明，在所有 研究的参数(十二烷基硫酸钠凝胶相对分子质量、等电点、 单抗交叉反应、激动剂亲和力、拮抗剂 配基结合的亲和力、立体特异性、激动剂的GTP位移 亲和力和受体密度)仅受体密度似乎 在9亿年的进化过程中逐渐改变 在高等物种中增加。毒碱受体已经被 从人脑、大鼠脑和心脏、猪心和 鲨鱼的大脑和心脏，以便比较 细节。毒鼠强与毒鼠强的进化关系 胆碱能受体和其他神经递质受体也是 正在研究中。蛋白质序列数据和定义的基因探针是 被用来跟踪肾上腺素能、胆碱能 和GABA能受体。我们已经克隆并测序了测试版 从人类和大鼠身上分离出一种 来自其他物种的克隆数量。特别是，一个积极的 已从果蝇基因组文库中分离出克隆。部分 序列数据显示，这个克隆包含一个50- 四个核苷酸，与相应的 人类Beta2序列。当序列被翻译成 氨基酸和有利的替代被考虑， 同源性高达100。尽管这件事的确切性质是 Beta2样基因目前尚不清楚，它可能为人类提供有价值的 有助于我们理解神经进化的信息 感受器。*(于1987年7月7日从LNP转来)。

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).