MECHANISMS OF OPIOID ACTION ON PEPTIDE RELEASE

描述：申请人摘要 阿片类药物与神经元上的受体相互作用，导致各种效应， 例如，在一个实施例中，镇痛欣快和利尿 然而，目前尚不清楚， 这些作用的主要靶点是神经元中的胞体和/或突触。 中枢神经系统 电活动和分泌活动， 下丘脑-神经垂体系统受到外源性 内源性阿片样物质 阿片类药物对细胞膜离子的特异性作用 然而，这些神经元和它们的神经末梢中的电导， 未知 加压素和催产素在体液平衡中起着至关重要的作用， 机制和各种生殖功能。 这些肽 神经激素由下丘脑的大细胞神经元合成 并由神经垂体末梢分泌。 而且 下丘脑-神经垂体系统发展耐受性和依赖性 吗啡在慢性给药期间表明， 系统是一个很好的模型，用于研究生理机制， 这些现象。 下丘脑-神经垂体系统提供了独特的 有机会解开阿片类药物在中枢神经系统的复杂作用 神经系统通过比较这种影响的不同组成部分， 中枢神经系统神经元 本文提出的研究目标是 确定介导阿片类药物诱导的修饰的膜机制 的神经激素分泌和反应的神经末梢与神经元 细胞体 为了实现这些目标，穿孔贴片记录 动作电位和Ca 2+和K+电流将由鉴定的， 分离的神经内分泌细胞和神经末梢， 成年大鼠下丘脑-神经垂体系统。 对释放的影响将 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，以确定如何急性阿片类药物的影响发生在 中枢神经系统神经元的胞体或终末。

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.