RUI: Anaphylatoxin Action in the Rat CNS

RUI：过敏毒素对大鼠中枢神经系统的作用

• 批准号: 8719732
• 负责人: Curtis Williams
• 金额: $ 19.09万
• 依托单位: SUNY College at Purchase
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-06-01 至 1992-11-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=8719732&HistoricalAwards=false
• 关键词: RUI; Anaphylatoxin; Action; Rat; CNS

Anaphylatoxins C3a and C5a are pharmacologically active peptides derived from the third and fifth components of serum complement. When administered focally to the rat hypothalamus, they mimic the neurotransmitters dopamine and norepinephrine in their respective abilities to modify standard behavioral tests. There are specific binding sites for both peptides on fresh brain slices and for C3a on synaptosome fractions (nerve terminal fractions in vitro). C5a has been shown to stimulate the release of both dopamine and norepinephrine from synaptosomes. Preliminary data obtained by high performance liquid chromatography indicate that C3a releases dopamine from synaptosomes of the striatal region of the forebrain. Dr. William's data are the first report of activities of the anaphylatoxins in the central nervous system. Further study of these phenomena may reveal their possible modulatory function in the brain. There are two main objectives in Dr. William's proposed studies. The first objective is to characterize the locations and mechanisms of neurotransmitter releasing activity in the brain. The release of neurotransmitter substances in vitro in the presence of blockers for calcium channels, GTP binding proteins and autoreceptors. The second objective is to associate the brain binding sites with specific nerve terminal types by immunocytochemistry and transmission electron microscopy.

过敏性毒素C3a和C5a是来源于血清补体第三组分和第五组分的药理活性多肽。当局部给药给大鼠下丘脑时，它们模仿神经递质多巴胺和去甲肾上腺素来改变标准的行为测试。这两种多肽在新鲜脑片上都有特异的结合部位，C3a在突触体组分(体外神经末梢部位)上也有特异的结合部位。研究表明，C5a可以刺激突触体释放多巴胺和去甲肾上腺素。高效液相色谱获得的初步数据表明，C3a从前脑纹状体区域的突触体内释放多巴胺。威廉博士的数据是关于过敏毒素在中枢神经系统中活动的第一份报告。对这些现象的进一步研究可能会揭示它们在大脑中可能的调节功能。威廉博士提议的研究有两个主要目标。第一个目标是确定神经递质释放活动在大脑中的位置和机制。在钙通道阻滞剂、GTP结合蛋白和自身受体存在的情况下，神经递质物质在体外的释放。第二个目标是通过免疫细胞化学和透射电子显微镜将脑结合部位与特定的神经末梢类型联系起来。