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 激素(CRF)与脑垂体起源[B-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 乙醇对下丘脑-垂体-肾上腺各水平的影响 轴(HPAA)，特别强调神经肽依赖事件。在……里面 在早期的研究中，我们已经确定了CRF和BE的特定结合位点 各种大鼠外周组织和牛嗜铬细胞的培养和 确定了CRF结合位点在大鼠肾上腺中的占有率 肝细胞膜与牛嗜铬细胞和Be的结合部位 膜激活腺苷环化酶/cAMP系统。此外，我们还拥有 证实CRF和BE的外周结合位点是由 糖皮质激素。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。 此外，CRF与大鼠垂体和红细胞膜的结合 在酒精暴露后下降。这些结果表明，变化 在CRF中，与红细胞膜的结合可能与垂体中的结合类似 膜。

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 hormone (CRF)] and pituitary origin [B-endorphin (BE) and adrenocorticotropin]. The long-term goal of these studies is to understand the effect of ethanol at each level of the hypothalamic-pituitary-adrenal axis (HPAA), with special emphasis on neuropeptide-dependent events. In earlier studies we have identified specific binding sites for CRF and BE in various rat peripheral tissues and bovine chromaffin cells in culture and established that occupancy of the CRF binding sites in rat adrenal membranes and bovine chromaffin cells and BE binding sites in hepatic membranes activate the adenylate cyclase/cAMP system. Furthermore, we have established that peripheral binding sites for CRF and BE are modulated by glucocorticoids. 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. Furthermore, CRF binding to rat pituitary and erythrocyte membranes was decreased following ethanol exposure. These results suggest that changes in CRF binding to erythrocyte membranes may parallel those in pituitary membranes.