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进一步了解 钙依赖性神经递质的细胞和膜方面 release. 脂质体将被用于向神经末梢递送物质， 已知或怀疑具有生理活性，难以或 因为没有这样的传递系统，所以不可能进行其他研究。 提高试剂对神经组织的靶向性， 这对于开发某些神经系统疾病的治疗方法是有用的。 疾病 该提案将利用我们的专业知识， 实验室，电生理学（青蛙运动神经的突触前功能 末端）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 用于将脂质体的包封内容物递送至马达的条件 神经末梢 2)脂质体通过什么机制传递其 内容物到运动神经末梢 作为推论， 重要性，就参与神经的功能而言 膜，其与脂质体膜的相互作用？ 3)是否Ca进入 是诱发ACh释放还是促进ACh释放所必需的？ 4)是 细胞对Ca、Sr和Ba的选择性是该过程固有的， 诱发ACh释放或它反映了钙从存储位移 网站？ 这个问题对于英航来说尤其重要， 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