Stimulation of bile duct epithelial secretion by glybenclamide in normal and cholestatic rat liver.

M H Nathanson; A D Burgstahler; A Mennone; J A Dranoff; L Rios-Velez

doi:10.1172/JCI2835

Liver Study Unit and Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06520, USA. michael.nathanson@yale.edu

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Liver Study Unit and Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06520, USA. michael.nathanson@yale.edu

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Liver Study Unit and Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06520, USA. michael.nathanson@yale.edu

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Liver Study Unit and Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06520, USA. michael.nathanson@yale.edu

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Liver Study Unit and Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06520, USA. michael.nathanson@yale.edu

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Published in Volume 101, Issue 12 on June 15, 1998
J Clin Invest. 1998;101(12):2665–2676. https://doi.org/10.1172/JCI2835.
© 1998 The American Society for Clinical Investigation

Published June 15, 1998 - Version history

Cholestasis is a cardinal complication of liver disease, but most treatments are merely supportive. Here we report that the sulfonylurea glybenclamide potently stimulates bile flow and bicarbonate excretion in the isolated perfused rat liver. Video-microscopic studies of isolated hepatocyte couplets and isolated bile duct segments show that this stimulatory effect occurs at the level of the bile duct epithelium, rather than through hepatocytes. Measurements of cAMP, cytosolic pH, and Ca2+ in isolated bile duct cells suggest that glybenclamide directly activates Na+-K+-2Cl- cotransport, rather than other transporters or conventional second-messenger systems that link to secretory pathways in these cells. Finally, studies in livers from rats with endotoxin- or estrogen-induced cholestasis show that glybenclamide retains its stimulatory effects on bile flow and bicarbonate excretion even under these conditions. These findings suggest that bile duct epithelia may represent an important new therapeutic target for treatment of cholestatic disorders.

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Stimulation of bile duct epithelial secretion by glybenclamide in normal and cholestatic rat liver.

M H Nathanson, A D Burgstahler, A Mennone, J A Dranoff, and L Rios-Velez

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Stimulation of bile duct epithelial secretion by glybenclamide in normal and cholestatic rat liver.

M H Nathanson, A D Burgstahler, A Mennone, J A Dranoff, and L Rios-Velez

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