The delta opioid receptor 1 is expressed by proliferating bile ductules in rats with cholestasis: Implications for the study of liver regeneration and malignant transformation of biliary epithelium
The delta opioid receptor 1 is expressed by proliferating bile ductules in rats with cholestasis: Implications for the study of liver regeneration and malignant transformation of biliary epithelium
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DOI：
10.1016/j.mehy.2005.06.019
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发表时间：
2005-01-01
影响因子：
4.7
通讯作者：
Bergasa, NV
中科院分区：
文献类型：
--
作者：
Nicoll, J;Axiotis, CA;Bergasa, NV
与正常成人肝脏形成鲜明对比的是，胎儿和大鼠肝脏以及胆管切除继发胆汁淤积大鼠的肝脏表达前脑啡肽原mRNA，其编码内源性阿片肽Met-脑啡肽。此外，在肝细胞中检测到 Met-enkephatin 免疫反应性；以及胆汁淤积大鼠肝脏中增殖的胆管。这些数据表明，在胆汁淤积中，内源性阿片类药物可能对胆汁淤积的肝脏产生局部作用。由于内源性阿片类药物通过与阿片类受体结合而发挥作用，因此胆汁淤积性肝脏中阿片类受体的存在将支持甲硫氨酸脑啡肽在原位发挥作用的假设。本手稿中提供的初步数据揭示了胆汁淤积大鼠肝脏中 δ 阿片受体的表达。这一发现表明，在某种情况下，甲硫氨酸脑啡肽可以与胆汁淤积肝脏中的阿片受体结合，发挥局部作用。使用阿片类激动剂和拮抗剂对这种胆汁淤积模型进行的体内研究将揭示阿片类药物调节肝再生的可能作用。在该动物模型中研究阿片拮抗剂对胆汁淤积演变的影响可能有助于深入了解肝再生机制。此外，由于一些与胆汁淤积和胆管增殖相关的病症可能因恶性肿瘤而复杂化，因此胆管系统恶性肿瘤中δ阿片受体的表达值得研究。 (c) 2005 Elsevier Ltd. 保留所有权利。
In sharp contrast with the normal adult liver, the fetal human and rat livers and the liver of rats with cholestasis secondary to bile duct resection express the preproenkephalin mRNA, which codes for the endogenous opioid peptide Met-enkephatin. Furthermore, Met-enkephatin immunoreactivity is detected in hepatocytes; and in proliferating bile ductules in the cholestatic rat liver. These data suggest that in cholestasis endogenous opioids may have a local effect in the cholestatic liver. As endogenous opioids exert their effect by binding to opioid receptors, the presence of opioid receptors in the cholestatic livers would support the hypothesis that Met-enkephatin plays a role in situ. Preliminary data presented in this manuscript reveals the expression of the delta opioid receptor in the liver of rats with cholestasis. This finding suggests that there is a scenario in which Met-enkephatin can bind to opioid receptors in the liver in cholestasis to exert a local effect. In vivo studies in this model of cholestasis with the use of opioid agonist and antagonist will shed light on the possible role of opioidergic regulation of liver regeneration. Studies on the effect of opiate antagonists on the evolution of cholestasis in this animal model may provide insight into the mechanisms of liver regeneration. In addition, as some conditions associated with cholestasis and bile ductular proliferation can be complicated by malignancy, the expression of the delta opioid receptor in malignant tumors of the biliary tree merits research. (c) 2005 Elsevier Ltd. All rights reserved.