ETHANOL-INDUCED CHANGES IN B-ENDORPHIN AND CRF BINDING TO PERIPHERAL TISSUE

尽管乙醇通常被认为是一种缓解焦虑的药物，但它的服用 模仿许多应激动作，涉及激活 下丘脑-垂体-肾上腺轴(HPAA)。对效果的理解 乙醇在这个轴线上的发展需要对中央和 外围调节因子及其相互作用，它们构成了 HPAA。与HPAA的动态平衡密切相关的有几个 脑源性神经肽(加压素和促肾上腺皮质激素释放 因子[CRF])和脑垂体起源(β-内啡肽[BE]和 促肾上腺皮质激素)。这些研究的长期目标是了解 乙醇在HPAA每个水平上的影响，特别强调 神经肽依赖事件。在评估酒精诱导的 对于CRF和BE的扰动，有必要验证是否存在 外周组织中特异的BE和CRF结合位点，并确定 如果这些受体的占据改变了已知的任何第二信使 系统。我们已经(1)使用125-I-rCRF确定了特定的结合位点 CRF在各种大鼠外周组织和牛嗜铬细胞中的表达 培养和(2)确定CRF结合位点占有率，在 在大鼠肾上腺膜和牛嗜铬细胞中最少，激活 腺苷环化酶/cAMP系统。此外，我们已经(1)使用 ~(125)I-人Be与不同大鼠外周血中Be的特异性结合 组织和(2)确定Be结合位点的占有率， 在大鼠肝细胞膜中最低，激活腺苷环化酶/cAMP 系统。大鼠暴露于乙醇蒸气14天的时间减少 免疫反应性血浆BE水平与降低CRF和BE结合 外周组织。此外，长期接触乙醇的大鼠 蒸气降低垂体CRF结合量、基础和CRF刺激的腺苷 循环酶活性和前阿片黑素皮质素信使RNA水平。

Although ethanol is commonly regarded as an anxiolytic, its administration mimics many actions of stress that involve activation of the hypothalamic-pituitary-adrenal axis (HPAA). An understanding of the effect of ethanol on this axis requires an appreciation of the central and peripheral regulatory factors and their interactions, which constitute the HPAA. Intimately involved in the homeostasis of the HPAA are several neuropeptides of brain origin (vasopressin and corticotropin-releasing factor [CRF]) and pituitary origin (beta-endorphin [BE] and adrenocorticotropin). The long-term goal of these studies is to understand the effect of ethanol at each level of the HPAA, with special emphasis on neuropeptide-dependent events. Before evaluating ethanol-induced perturbations of CRF and BE, it was necessary to validate the existence of specific BE and CRF binding sites in peripheral tissues, and to determine if occupancy of these receptors altered any of the known second-messenger systems. We have (1) identified, using 125-I-rCRF, specific binding sites for CRF in various rat peripheral tissues and bovine chromaffin cells in culture and (2) established that occupancy of the CRF binding sites, at least in rat adrenal membranes and bovine chromaffin cells, activates the adenylate cyclase/cAMP system. Furthermore, we have (1) identified, using 125-I-human BE, specific binding sites for BE in various rat peripheral tissues and (2) established that occupancy of the BE binding sites, at least in rat hepatic membranes, activates the adenylate cyclase/cAMP system. Exposure of rats to ethanol vapor for 14 days lowered immunoreactive plasma BE levels and reduced CRF and BE binding to a variety of peripheral tissues. In addition, chronic exposure of rats to ethanol vapors lowered pituitary CRF binding, basal and CRF-stimulated adenylate cyclase activity, and pro-opiomelanocortin messenger RNA levels.