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胆管细胞分泌的调节

Regulation of cholangiocyte secretion.

作者信息

Fitz J Gregory

机构信息

Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.

出版信息

Semin Liver Dis. 2002 Aug;22(3):241-9. doi: 10.1055/s-2002-34502.

Abstract

Observations from a variety of model systems suggest that ductular bile formation is mediated in large part by transepithelial transport of Cl(-) ions and have identified Cl(-) channels in the apical membrane as important targets for hormones and other factors that modulate bile volume and composition through effects on duct cells. Signaling through secretin receptors that stimulate adenylyl cyclase and activate the cystic fibrosis transmembrane regulator (CFTR) Cl(-) channels represents a prototype for cholangiocyte secretion. However, recent observations indicate that cholangiocytes also express a variety of receptors that modulate secretory responses in the absence of effects on cyclic adenosine monophosphate (cAMP), and Cl(-) channels unrelated to CFTR have been identified. Moreover, rapid exocytosis of subapical vesicles is coupled closely to different Cl(-) secretory responses. These observations suggest that the protein composition of the apical domain is regulated by selective exocytosis and endocytosis of channel-containing vesicles, leading to rapid modulation of the transport capacity of individual cells in response to changing physiologic demands.

摘要

来自各种模型系统的观察结果表明,胆小管胆汁形成在很大程度上是由Cl⁻离子的跨上皮运输介导的,并且已经确定顶端膜中的Cl⁻通道是激素和其他通过影响胆管细胞来调节胆汁体积和成分的因子的重要靶点。通过刺激腺苷酸环化酶并激活囊性纤维化跨膜调节因子(CFTR)Cl⁻通道的促胰液素受体发出信号,是胆管细胞分泌的一个原型。然而,最近的观察表明,胆管细胞还表达多种受体,这些受体在不影响环磷酸腺苷(cAMP)的情况下调节分泌反应,并且已经鉴定出与CFTR无关的Cl⁻通道。此外,顶端下小泡的快速胞吐作用与不同的Cl⁻分泌反应密切相关。这些观察结果表明,顶端结构域的蛋白质组成受含通道小泡的选择性胞吐作用和内吞作用调节,从而导致单个细胞的运输能力根据生理需求的变化而快速调节。

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