ADENOSINE DERIVATIVES AND CHOLINERGIC NERVE ENDINGS

腺苷衍生物和胆碱能神经末梢

• 批准号: 3394983
• 负责人: EUGENE M SILINSKY
• 金额: $ 10.1万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-05-01 至 1989-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3394983
• 关键词: acetylcholine; adenosine triphosphate; bioassay; bioluminescence; cations; cyclic nucleoside monophosphate; electrophysiology; fresh water environment; liposomes; motor neurons; nerve endings; neurochemistry; neuromuscular transmission; parasympathetic nervous system; peripheral nervous system

The aim of this project is to study further the involvement of adenosine derivatives in the function of cholinergic nerve endings in the peripheral nervous system. With respect to the release of adenine nucleotide, is there an association between all forms of acetylcholine (ACh) secretion and the release of adenosine triphosphate (ATP). Specifically, ACh release will be evoked by various methods and the release of ATP and ACh assayed. Bioassay chemical methods will be used to detect ACh release and the firefly bioluminescence reaction employed to detect ATP release. With respect to the effects of adenosine derivatives, an electrophysiological study of ACh release will be made to characterize the specific adenosine receptors that mediate inhibition and enhancement of ACh release at motor nerve endings and the putative adenosine phosphate receptors that inhibit ACh release at preganglionic nerve endings. The potency sequences for various agonists and antagonists and the relationship between adenosine or purinergic receptor activation and intracellular modulators such as Ca and cyclic necleotides will be investigated. Liposomes will be employed as a means of delivering Ca or purine derivatives to the cytoplasm of the nerve ending. As abnormal adenine necleotide metabolism occurs in certain forms of muscle disease (e.g. Duchenne dystrophy), and ACh release is impaired at ganglia in familial dysautonomia, studying the normal relationship between adenosine derivatives and neuromuscular function should provide a valuable framework for future studies on the diseased cholinergic synapses.

本项目的目的是进一步研究腺苷参与 在外周胆碱能神经末梢功能中的作用 神经系统 关于腺嘌呤核苷酸的释放， 所有形式的乙酰胆碱（ACh）分泌之间存在关联， 三磷酸腺苷（ATP）的释放。 具体来说，ACh释放 用各种方法诱发，测定ATP和ACh的释放。 生物测定化学方法将用于检测乙酰胆碱释放和 萤火虫生物发光反应用于检测ATP释放。 与 关于腺苷衍生物的作用， 将进行ACh释放的研究以表征特异性腺苷 运动时介导ACh释放抑制和增强的受体 神经末梢和假定的磷酸腺苷受体， 节前神经末梢的乙酰胆碱释放。 的效力序列 各种激动剂和拮抗剂以及腺苷或 嘌呤能受体活化和细胞内调节剂如Ca和 将研究环状核苷酸。 脂质体将被用作 将Ca或嘌呤衍生物递送至神经细胞质的手段 结局 由于腺嘌呤核苷酸代谢异常， 肌肉疾病（如杜氏营养不良），乙酰胆碱释放受损， 神经节在家族性自主神经功能障碍，研究正常的关系， 腺苷衍生物和神经肌肉功能应该提供有价值的 为今后研究胆碱能突触疾病提供了框架。