EVOLUTION OF NEUROTRANSMITTER RECEPTORS

该项目的目的是检查结构和功能 神经递质受体蛋白的进化。 使用毒蕈碱 胆碱能受体作为我们分离的初始模型系统， 表征了来自大脑的毒蕈碱乙酰胆碱受体， 各种物种的心脏 大脑和心脏组织 从包括哺乳动物，鸟类，爬行动物， 两栖动物和鱼类。 此外，包括昆虫在内的低等物种 （果蝇）提供了受体。 正在进行的研究表明， 所有研究的参数; 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、立体特异性、GTP位移和受体密度，只有 最后一个参数，受体密度，似乎已经改变了增加 历经9亿年的进化 毒蕈碱受体正从人脑、大鼠脑和 心脏，猪心和鲨鱼的大脑和心脏，以详细比较 主要结构。 毒蕈碱与 胆碱能受体和其他神经递质受体也被 研究了 蛋白质测序和基因探针将用于跟踪 肾上腺素能、胆碱能、多巴胺能、多巴胺能、GABA能的演变 和阿片受体蛋白。 神经递质生物合成/降解酶，例如酪氨酸 羟化酶、CAT、乙酰胆碱酯酶将用单克隆抗体进行检查。 任何进化/结构的抗体和一级序列数据 与神经递质受体蛋白的关系。

The purpose of this project is to examine the structural and functional evolution of neurotransmitter receptor proteins. Using muscarinic cholinergic receptors as the initial model system we have isolated and characterized the muscarinic acetylcholine receptor 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. In addition, lower species including insects (drosophila) have provided receptors. The studies underway indicate that all of the studied parameters; SDS gel molecular weight, isoelectric points, monoclonal antibody cross reactivity, agonist affinity, antagonist affinity, stereospecificity, GTP shifts, and receptor density, only the last parameter, receptor density, appears to have changed by increasing gradually over 900 million years of evolution. Muscarinic receptors are being purified from human brain, rat brain and heart, pig heart and shark brain and heart in order to compare in detail primary structures. The evolutionary relationship between muscarinic cholinergic receptors and other neurotransmitter receptors is also being studied. Protein sequencing and gene probes will be used to follow the evolution of adrenergic, cholinergic, dopaminergic, serotonergic, GABAergic and opiate receptor proteins. Neurotransmitter biosynthetic/degradative enzymes, e.g. tyrosine hydroxylase, CAT, acetylcholinesterase will be examined with monoclonal antibodies and primary sequence data for any evolutionary/structural relationship with the neurotransmitter receptor proteins.