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，在无脊椎动物神经组织中存在并进化了基本的鸦片类信号传递过程，并在进化中保留在人类身上。我们的初步发现支持这一点，即无脊椎动物产生一种内源性吗啡样物质，并具有与人类同类产品难以区分的mu3阿片受体。该方案中的实验旨在识别吗啡本身，克隆无脊椎动物神经系统中的mu3受体，并将这些发现直接与功能测试相关联，即吗啡刺激的钙瞬变。我们建议解决以下目标：阿片类生物碱，即吗啡在无脊椎动物神经系统中的作用是什么，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。我们建议用海洋双壳类紫贻贝的神经组织来发展这一假说，使其成为分析的模型。更具体地说，这些研究测试了我们的假设，即阿片信号超越疼痛功能，在无脊椎动物中进化来减少感觉输入，而且由于这个系统运行得如此好，它在进化过程中被保留了下来。鉴于越来越多的文献表明内源性吗啡在神经信号传递中的作用，它参与精神病学的潜力变得越来越明显。