EFFECT OF ETHANOL ON POMC PEPTIDE SYNTHESIS AND RELEASE IN VIVO AND IN VITRO

内源性神经肽构成了一个不断增长的生物学清单 具有中心和外围位置的重要分子 合成的作用和轨迹。尽管显然重要的是 具有调节内分泌和免疫调节功能的生物活性多肽 神经事件，缺乏对其影响的详细评估 乙醇甚至在一个神经肽系统上也是如此。自.以来 众所周知，乙醇的使用会改变某些监管规定 下丘脑-垂体-肾上腺轴(HPAA)和 由于这个系统的完整性有赖于综合和 特定调节性神经肽的分泌 下丘脑(如促肾上腺皮质激素释放激素(CFR)； 加压素)和脑下垂体(如β内啡肽；促肾上腺皮质激素) 水平，我们一直在评估乙醇对 HPAA作为体内和体外的模型系统。实现这一目标 了解直接和间接影响的必要性 乙醇在细胞水平上，我们一直在研究ATT-20 细胞、促肾上腺皮质激素和促黑素细胞培养和乙醇- 暴露完整的雄性大鼠。研究其影响是可能的。 乙醇在主要信号转导系统上的作用 腺苷环化酶(AC)/环(C)AMP系统 肌醇磷脂蛋白激酶C系统。据设想， 对HPAA的每个组成部分的探索(即， 中枢神经系统、脑垂体腺和肾上腺)相互独立 随后将完整的动物意志的结果进行积分 使人能够描述急性、慢性、直接和间接 乙醇在细胞和亚细胞水平上的影响，以及 乙醇诱导的原发部位与次级部位 HPAA的摄动。因为神经内分泌细胞 不断合成和分泌产品，我们的研究在 他们最宽泛的意义是为了理解 乙醇对分泌物刺激-分泌-合成偶联的影响 细胞。到目前为止，我们的调查已经产生了各种不同的 信息。

Endogenous neuropeptides constitute a growing list of biologically important molecules with both central and peripheral sites of action and loci of synthesis. In spite of the obvious importance of biologically-active peptides in regulating both endocrine and neural events, lacking is a detailed evaluation of the effects of ethanol on even a single neuropeptide system. Since the administration of ethanol is known to alter certain regulatory aspects of the hypothalamic-pituitary-adrenal axis (HPAA) and since the integrity of this system depends on the synthesis and secretion of specific regulatory neuropeptides at the hypothalamic (e.g., corticotropin-releasing hormone (CFR); vasopressin) and pituitary gland (e.g., beta endorphin (BE); ACTH) level, we have been evaluating the impact of ethanol on the HPAA as a model system in vivo and in vitro. Realizing the necessity of understanding the direct versus indirect effects of ethanol at the cellular level, we have been working with AtT-20 cells, corticotropes, and melanotropes in culture and ethanol- exposed intact male rats. It has been possible to study the effects of ethanol on such primary signal transduction systems as the adenylate cyclase (AC)/cyclic (c) AMP system and the phosphoinositide protein kinase C system. It is envisioned that the exploration of each of the component parts of the HPAA (i.e., CNS, pituitary and adrenal gland) independent of one another and the subsequent intergration of results from the intact animal will enable one to profile the acute, chronic, direct and indirect effects of ethanol at the cellular and subcellular level, as well as the primary versus secondary sites of ethanol-induced perturbations of the HPAA. Since neuroendocrine cells are continuously synthesizing and secreting products, our studies in their broadest sense are designed to understand the effects of ethanol on stimulus-secretion-synthesis coupling in secretory cells. To date our investigations have yielded a variety of information.