NEUROTRANSMITTER RELEASE USING LIPOSOMES

使用脂质体释放神经递质

• 批准号: 3417714
• 负责人: EUGENE M SILINSKY
• 金额: $ 22.81万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-07-01 至 1995-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3417714
• 关键词: Rana; acetylcholine; barium; calcium; calcium channel; calmodulin; cytoplasm; drug delivery systems; electron microscopy; electrophysiology; endocytosis; fluorescence microscopy; fluorescent dye /probe; inositol phosphates; liposomes; magnesium; membrane activity; membrane permeability; neuroimmunomodulation; neurotransmitter metabolism; neurotransmitters; second messengers; strontium; synapses; synapsins; voltage /patch clamp; voltage gated channel

The overall objective of the proposed research is to further our knowledge of the cellular and membrane aspects of calcium-dependent neurotransmitter release. Liposomes will be used to deliver to nerve terminals substances, known or suspected to be physiologically active, which are difficult or impossible to study otherwise because of absence of such a delivery system. Improving the targeting of reagents to neural tissue could someday prove useful for the development of treatments for some classes of neurological diseases. The proposal will exploit the combined expertise of our laboratories, electrophysiology (presynaptic function at frog motor nerve endings) and membranology (development and applications of liposomes). It is designed to answer the following questions: 1) What are the optimal conditions for delivering the encapsulated contents of liposomes to motor nerve endings? 2) What is the mechanism by which liposomes deliver their contents to motor nerve terminals? As a corollary, what is the significance, with respect to the function of the participating nerve membrane, of its interaction with the liposomal membrane? 3) Is Ca entry required for evoked ACh release or for facilitation of ACh release? 4) Is the cellular selectivity for Ca, Sr and Ba intrinsic to the process of evoked ACh release or does it reflect the displacement of Ca from storage sites? This question is particularly important with respect to Ba, which is used in patch clamp studies. 5) Are second messenger systems (e.g., inositol tris phosphate, calmodulin, synapsin I) involved in modulation of neurotransmitter release?

拟议研究的总体目标是加深我们的知识 钙依赖性神经递质的细胞和膜方面 发布。 脂质体将用于将物质输送到神经末梢， 已知或怀疑具有生理活性，这是困难或 由于缺乏这样的传递系统，不可能以其他方式进行研究。 有一天，改进试剂对神经组织的靶向性可能会被证明 对于开发某些类型的神经系统疾病的治疗方法很有用 疾病。 该提案将利用我们的综合专业知识 实验室，电生理学（青蛙运动神经的突触前功能） 结局）和膜学（脂质体的开发和应用）。 它 旨在回答以下问题：1）什么是最佳的 将脂质体封装的内容物递送至运动的条件 神经末梢？ 2）脂质体的传递机制是什么？ 运动神经末梢的内容？ 作为推论，什么是 就参与神经的功能而言具有重要意义 膜，它与脂质体膜的相互作用？ 3）Ca是否进入 诱发乙酰胆碱释放或促进乙酰胆碱释放所需？ 4) 是 细胞对 Ca、Sr 和 Ba 的选择性 诱发 ACh 释放还是反映了 Ca 从储存中的置换 网站？ 这个问题对于 Ba 来说尤其重要， 用于膜片钳研究。 5）是第二信使系统（例如， 肌醇三磷酸、钙调蛋白、突触蛋白 I) 参与调节 神经递质释放？