MECHANISMS OF OPIOID ACTION ON PEPTIDE RELEASE

阿片类药物对肽释放的作用机制

• 批准号: 6150475
• 负责人: JOSE R LEMOS
• 金额: $ 21.28万
• 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/6150475
• 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：申请人的摘要 阿片类药物与神经元上的受体相互作用，导致各种作用， 例如，镇痛，欣快和利尿。 但是，尚不知道，是否 这些效果的主要目标是在somata和/或突触中 中枢神经系统。 电气和分泌活动 下丘脑 - 神经型植物学系统受外源和 内源性阿片类药物。 阿片类药物对膜离子的特定作用 然而，这些神经元及其神经终末的电导是 未知。 加压素和催产素在液体稳态中具有至关重要的作用 机理和各种生殖功能。 这些肽 神经激素是由下丘脑的巨细胞神经元合成的 并从神经型物理末端分泌。 此外， 下丘脑 - 神经型植物学系统具有耐受性和依赖性 长期给药期间的吗啡表明这种中枢神经 系统是研究生理机制的良好模型 这些现象。 下丘脑 - 神经植物学系统提供了独特的 揭示中央阿片类药物的复杂作用的机会 神经系统通过比较对不同组成部分的影响 中枢神经系统神经元。 这里提出的研究的目的是 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终末的反应与神经元的反应 细胞体。 为了实现这些目标，穿孔的贴片录音 动作电位以及Ca2+和K+电流的确定性将由确定的， 孤立的神经内分泌细胞和神经末端从 成年大鼠的下丘脑神经型物理系统。 对释放的影响将 通过使用 放射免疫测定和电容测量。 这些研究会 提供一个独特的机会来确定急性阿片类药物的影响 中枢神经系统神经元的SOMATA和或终末。