MECHANISMS OF OPIOID ACTION ON PEPTIDE RELEASE

阿片类药物对肽释放的作用机制

• 批准号: 2623443
• 负责人: JOSE R LEMOS
• 金额: $ 23.15万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-03-15 至 2003-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2623443
• 关键词: action potentials; calcium channel; endogenous opioid; hormone regulation /control mechanism; hypothalamic pituitary axis; laboratory rat; neurons; neuropharmacology; neuroregulation; opioid receptor; oxytocin; potassium channel; vasopressins; voltage /patch clamp; voltage gated channel

DESCRIPTION: Applicant's Abstract Opioids interact with receptors on neurons, leading to a variety of effects, e.g., analgesia, euphoria, and diuresis. It is not known, however, whether the primary target for these effects are at somata and/or synapses in the central nervous system. The electrical and secretory activities of the hypothalamo-neurohypophysial system are affected by both exogenous and endogenous opioids. The specific effects of opioids on membrane ionic conductances in these neurons and their nerve terminals, however, are unknown. Vasopressin and oxytocin have crucial roles in fluid homeostatic mechanisms and in various reproductive functions. These peptide neurohormones are synthesized by magnocellular neurons of the hypothalamus and secreted from neurohypophysial terminals. Furthermore, the hypothalamo-neurohypophysial system develops tolerance and dependence to morphine during chronic administration suggesting that this central nervous system is a good model for studying the physiological mechanisms underlying these phenomena. The hypothalamo-neurohypophysial system affords the unique opportunity of unraveling the complicated effects of opioids in the central nervous system by comparing such effects on the different components of central nervous system neurons. The goal of the research proposed here is to determine membrane mechanisms that mediate opioid-induced modifications of neurohormone secretion and the responses of nerve terminals vs. neuronal cell bodies. To achieve these objectives, perforated patch recordings of action potentials and of Ca2+ and K+ currents will be made from identified, isolated neuroendocrine cells and nerve terminals obtained from the hypothalamo-neurohypophysial system of adult rats. Effects on release will be compared between magnocellular neurons and NH terminals by the use of radioimmununoassays and capacitance measurements. These studies will provide a unique opportunity to determine how acute opioid effects occur at the somata and or terminals of central nervous system neurons.

描述：申请者摘要 阿片类药物与神经元上的受体相互作用，导致多种效应， 例如，止痛、兴奋和利尿。然而，目前尚不清楚， 这些效应的主要靶点是胞体和/或突触。 中枢神经系统。人的电活动和分泌活动 下丘脑-神经垂体系统受外源性和 内源性阿片类药物。阿片类药物对膜离子的特异性影响 然而，这些神经元及其神经末梢的电导是 未知。加压素和催产素在体液平衡中起着至关重要的作用 在生殖机制和各种生殖功能中发挥作用。这些多肽 神经激素是由下丘脑的大细胞神经元合成的 并由神经垂体终末分泌。此外， 下丘脑-神经垂体系统对 长期服用吗啡表明这种中枢神经系统 系统是一个很好的模型来研究潜在的生理机制 这些现象。下丘脑-神经垂体系统提供了独特的 解开阿片类药物在中部地区复杂影响的机会 通过比较这些对神经系统不同成分的影响 中枢神经系统神经元。这里提出的研究目标是 确定介导阿片类药物诱导的修饰的膜机制 神经激素分泌和神经末梢与神经元的反应 细胞体。为了实现这些目标，穿孔的补丁记录 动作电位以及钙和钾电流将由识别的， 分离的神经内分泌细胞和神经末梢来自 成年大鼠下丘脑-神经垂体系统。对释放遗嘱的影响 在大细胞神经元和NH终末之间进行比较 放射免疫测定和电容测量。这些研究将 提供了一个独特的机会来确定急性阿片类药物效应是如何在 中枢神经系统神经元的体细胞和或终末。