INVERTEBRATE MODEL FOR ENDOGENOUS MORPHINE PROCESSES

内源吗啡过程的无脊椎动物模型

• 批准号: 6494856
• 负责人: GEORGE B STEFANO
• 金额: $ 20.94万
• 依托单位: COLLEGE AT OLD WESTBURY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-01 至 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6494856
• 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，基本的鸦片信号传导过程存在并进化于无脊椎动物神经组织，并已在人类中进化保留。这是我们的初步发现支持的，即无脊椎动物会产生内源性吗啡样材料，并具有与人类对应物无法区分的Mu3鸦片受体。该提案中的实验旨在鉴定吗啡本身，在无脊椎动物神经系统中克隆MU3受体，并将这些发现与功能测试（即吗啡刺激的钙瞬变）直接相关。我们建议解决以下目标：鸦片生物碱（即吗啡）在无脊椎动物神经系统中的作用是什么？它告诉我们有关人类系统的什么作用？本提案中的实验旨在回答这些问题。我们建议通过海洋双壳类Mytilus Edulis的神经组织提出这一假设，使其成为该分析的模型。更具体地说，这些研究检验了我们的假设，即鸦片信号传导，超越疼痛功能，在无脊椎动物中演变以减少感觉输入，并且由于该系统效果很好，因此在进化过程中保留了它。鉴于内源性吗啡在神经信号中的日益增长的文献，其参与精神病学的潜力变得显而易见。