RUI: Anaphylatoxin Action in the Rat CNS

过敏毒素C3a和C5a是从血清补体的第三和第五组分中提取的具有药理活性的肽。当局部给药于大鼠下丘脑时，它们模仿神经递质多巴胺和去甲肾上腺素各自的能力来修改标准的行为测试。两种肽在新鲜脑切片上和C3a在突触体部分（体外神经末梢部分）上都有特定的结合位点。C5a已被证明能刺激突触体释放多巴胺和去甲肾上腺素。通过高效液相色谱法获得的初步数据表明，C3a从前脑纹状体区突触体释放多巴胺。威廉博士的数据是关于过敏毒素在中枢神经系统活动的第一份报告。对这些现象的进一步研究可能揭示它们在大脑中可能的调节功能。威廉博士提出的研究有两个主要目标。第一个目标是描述大脑中神经递质释放活动的位置和机制。神经递质物质在钙通道阻滞剂、GTP结合蛋白和自身受体存在下的体外释放。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位点与特定的神经末梢类型联系起来。

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.