Aquaporin water channels in liver: Their significance in bile formation

✍ Scribed by Raul A. Marinelli; Nicholas F. LaRusso

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 140 KB
• Volume: 26
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.510260539

✦ Synopsis

HEPATOLOGY Concise Review called AQP-CD, is the vasopressin-regulated water channel Aquaporin Water Channels in of the renal collecting duct (hence, CD) apical membrane. 9,10 AQP3 and AQP4 (or MIWC for mercury-insensitive water Liver: Their Significance channel) are both located in the basolateral membranes of epithelial cells of distal colon, trachea, and also in renal col-in Bile Formation lecting duct, but are not vasopressin-responsive. We have recently found that the messenger RNA for AQP4 is present in cholangiocytes (Marinelli RA, Pham L, LaRusso NF, un-RAU ´L A. MARINELLI AND NICHOLAS F. LARUSSO published data, June 1997). AQP5 is abundant in lung, lachrymal, and salivary glands. 11 AQP0 is the major intrinsic Bile is primarily elaborated by hepatocytes and subseprotein expressed in lens fiber cells, where it comprises over quently delivered to the intrahepatic bile ducts, where it is 60% of the membrane protein. 12 modified by cholangiocytes, the epithelial cells that line the

The presence of AQPs markedly increases cell membrane biliary tree. Cholangiocytes, as polarized epithelial cells, poswater permeability facilitating rapid movement of water in sess highly specialized basolateral and apical membrane doresponse to small osmotic gradients. However, the physiologmains with different transport systems involved in the vectoical relevance of these water-transporting proteins may reside rial movement of solutes and osmotically driven water primarily in providing the cell a potential mechanism for molecules. These membrane transporters include a family controlling water permeability by regulating the number of of recently identified water-selective channel proteins known AQP molecules in the membrane. Deficiency or alterations of as aquaporins (AQPs). In this review, we provide a brief AQP function should result in abnormal physiology; indeed, summary of what is known about AQPs and their functional mutations of the AQP2 gene are responsible for the syndrome significance in the transport of water by the liver and in the of autosomal recessive nephrogenic diabetes insipidus. Inelaboration of bile.

terestingly, null mutations in the AQP1 gene, recently identified in a few individuals, are not associated with clinically THE AQP FAMILY OF WATER CHANNELS apparent disease. Nevertheless, the expression of other wa-Six mammalian AQPs, numbered 0 to 5, have been identiter channels or adaptations in the transport of solutes may fied thus far. Biochemical and structural studies indicate compensate for AQP1 deficiency in those individuals. that AQPs consist of six bilayer-spanning a-helices connected by three extracellular (A, C, and E) and two intracellu-

MEMBRANE WATER TRANSPORT IN HEPATOCYTES:

ever, as we discuss below, the liver appears to be an exception LIPID PATHWAY in that AQP1 is regulated in cholangiocytes. AQP2, initially Molecular studies from our laboratory and others indicate that none of the identified AQPs are expressed in hepato-Abbreviations: AQP, aquaporin; CFTR, cystic fibrosis transmembrane regulator. cytes. 15,16 We have also performed functional (biophysical)

From the Center for Basic Research in Digestive Diseases, Division of Gastroenterolstudies to determine the pathways by which water moves ogy and