INVERTEBRATE MODEL FOR ENDOGENOUS MORPHINE PROCESSES

内源吗啡过程的无脊椎动物模型

• 批准号: 6146642
• 负责人: GEORGE B STEFANO
• 金额: --
• 依托单位: COLLEGE AT OLD WESTBURY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-15 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6146642
• 关键词: Bivalvia; alternatives to animals in research; biological models; biological signal transduction; calcium flux; minority institution research support; model design /development; molecular cloning; morphine; opioid receptor; pain

Our hypothesis is that fundamental opiate signaling processes exist and evolved in invertebrate neural tissues and have been evolutionarily retained in humans. This is supported by our preliminary findings that invertebrates produce an endogenous morphine-like material and have mu3 opiate receptors which are indistinguishable from the human counterpart. The experiments in this proposal are designed to identify morphine itself, clone the mu3 receptor in the invertebrate nervous system and directly relate these findings to a function test, i.e., morphine stimulated calcium transients. We propose to address the following objectives: What is the role of the opiate alkaloid, i.e., morphine in the invertebrate nervous system and what does it tell us about the human system? The experiments in this proposal are designed to answer these questions. We propose to develop this hypothesis with the neural tissues of the marine bivalve Mytilus edulis, making it a model for this analysis. More specifically, these studies test our hypothesis that opiate signaling, transcending pain functions, evolved in invertebrates to diminish sensory inputs, and that because this system worked so well, it was retained during evolution. Given this growing documentation for endogenous morphine in neural signaling the potential for its involvement in psychiatry is becoming evident.

我们的假设是，基本的阿片信号传导过程存在于无脊椎动物的神经组织中并在进化中保留在人类中。我们的初步研究结果支持这一点，即无脊椎动物产生内源性吗啡样物质，并具有与人类对应物无法区分的mu3阿片受体。本提案中的实验旨在鉴定吗啡本身，克隆无脊椎动物神经系统中的mu3受体，并将这些发现与功能测试直接相关，即，吗啡刺激钙瞬变。我们建议解决以下目标：阿片类生物碱的作用是什么，即，无脊椎动物神经系统中的吗啡，它告诉我们关于人类系统的什么？本提案中的实验旨在回答这些问题。我们建议发展这一假设与海洋双壳贝类紫贻贝的神经组织，使其成为这种分析的模型。更具体地说，这些研究验证了我们的假设，即阿片信号，超越疼痛功能，在无脊椎动物中进化以减少感觉输入，并且因为这个系统工作得很好，所以它在进化过程中被保留下来。鉴于越来越多的文献证明内源性吗啡在神经信号传导中的作用，其在精神病学中的作用越来越明显。