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Effects of Neurotransmitters on Acetylcholine Release in the Brain-In Vivo Dealysis

神经递质对脑体内脱氢乙酰胆碱释放的影响

基本信息

批准号：
63480192
负责人：
KATAYAMA Sadao
金额：
$ 1.28万
依托单位：
Hiroshima University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1988
资助国家：
日本
起止时间：
1988 至 1990
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-63480192/
关键词：
Mammalian brain Acetylcholine release In vivo intracerebral dialysis Neuropeptide Neurotransmitter interactions 哺乳類頭アセチルコリン in vivo dialysis法海馬線条体ドパミン LHーRH 神経伝達物質遊離 in vivo dialysis 大脳皮質コリン作働薬加齢 nerve growth factor

项目摘要

Acetylocholine (ACh) has been considered to be involved in the higher brain function such as learning and memory in the cerebral cortex and hippocampus, while in the basal ganglia and cerebellum it has relations with movement. It is important to elucidate the turnover of ACh in the brain not only inthe basic neuroscience but also for understanding of pathophysilogy and treatment of neurodegenerative disorders such as Alzheimer's disease. In this research project, we established the method for measuring ACh contents from in vivo dialysis samples of the brain. By use of method, the effects of various neurotransmitters and drugs on the release of ACh were studied in the rat brain.First, we estabilished the method for measuring the endogenous ACh release in the striatum and hippocampus. The dialysis probe which was equipped with a semipermeable tube, was inserted into the rat brain. On perfusion experiments, rats were allowed to move freely and perfused with a Ringer solution. The perfusat … More es were collected with 20-min intervals and, ACh contents were measured by HPLC. When perfused with a Ringer solution, ACh contents were very low and not detectable. On the other hand, they were able to be detected in the presence of an anticholinesterase, physostigmine. Thus, we confirmed that ACh in the perfusates was released from cholinergic nerve terminals. As the next step, effects of neuropeptides, cholinergic drugs and nerve growth factor on ACh release were studied. Peripheraly administration of cholecystokinin induced an increase of ACh release in the striatum, and the results suggested that the action of the peptide was, in part, mediated via vagal afferent impulses. Neurotensin did not affect the striatal cholinergic release, while it increased the release of dopamine and its metabolites. A muscarinic ACh receptor agonist inhibited the release of ACh in the striatum, whereas an antagonist stimulated it. In addition, LH-RH had no effect on the hippocampal ACh release, while it decreased the release of glutamate.In summary, the mechanisms of ACh release and its modulation by other neuroactive substances were investigated in the rat brain. Since the experimental system is in vivo, these results have possibilities for application to drug development. Less

乙酰胆碱（Acetylocholine，ACh）在大脑皮层和海马中被认为与学习记忆等高级脑功能有关，而在基底节和小脑中则与运动有关。阐明ACh在脑中的周转不仅在基础神经科学中而且对于理解病理生理学和治疗神经退行性疾病如阿尔茨海默病都是重要的。本研究建立了在体脑透析标本中乙酰胆碱含量的测定方法。本研究应用该方法研究了多种神经递质和药物对大鼠脑内ACh释放的影响。首先建立了测定纹状体和海马内源性ACh释放的方法。将配有半透性管的透析探针插入大鼠脑内。在灌注实验中，允许大鼠自由移动并用林格氏溶液灌注。灌注液 ...更多信息每隔20 min收集一次样品，用HPLC法测定乙酰胆碱含量。用林格氏液灌流时，ACh含量很低，检测不到。另一方面，它们能够在抗胆碱酯酶剂毒扁豆碱的存在下被检测到。因此，我们证实，ACh在灌注液中释放胆碱能神经末梢。作为下一步，神经肽，胆碱能药物和神经生长因子对乙酰胆碱释放的影响进行了研究。外周给药胆囊收缩素诱导增加乙酰胆碱释放在纹状体，结果表明，该肽的作用，在一定程度上，通过迷走神经传入冲动介导。神经降压素不影响纹状体胆碱能的释放，但增加多巴胺及其代谢产物的释放。胆碱能受体激动剂抑制纹状体ACh的释放，而胆碱能受体拮抗剂则刺激纹状体ACh的释放，LH-RH对海马ACh的释放无影响，但能减少谷氨酸的释放。由于实验系统是在体内，这些结果有可能应用于药物开发。少