Effect of endotoxin on bile acid transport in rat liver - a potential model for sepsis-associated cholestasis. Moseley, Richard H., Wei Wang, Hiroaki Takeda, Kenneth Lown, Lawton Shick, M. Ananthanarayanan, and Frederick J. Suchy. Division of Gastroenterology, Department of Internal Medicine, Veterans Affairs Medical Center and University of Michigan School of Medicine, Ann Arbor, Michigan and Pediatric Gastroenterology/Hepatology Section, Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut
APStracts 3:0025G, 1996.
Intrahepatic cholestasis in the setting of extrahepatic bacterial infection has been attributed to the effects of endotoxin and cytokines, such as tumor necrosis factor [alpha] (TNF[alpha]), on bile acid transport. To define the mechanism of sepsis-associated cholestasis, taurocholate transport was examined in basolateral (blLPM) and canalicular (cLPM) rat liver plasma membrane vesicles derived from control and endotoxin (LPS)-treated animals and in plasma membrane vesicles prepared following TNF[alpha]-treatment. Na+-dependent [3H]taurocholate uptake and both membrane-potential and ATP-dependent [3H]taurocholate transport were reduced in blLPM and cLPM vesicles, respectively, following LPS treatment. In membrane vesicles from TNF[alpha]-treated animals, Na+-dependent [3H]taurocholate uptake was also reduced. Northern blot hybridization, using cDNA probes for the putative sinusoidal bile acid transporter (Ntcp) and canalicular ecto-ATPase, demonstrated decreased mRNA levels following LPS and TNF[alpha] treatment. Immunoblot analysis of membrane extracts from LPS-treated animals revealed decreased levels of these putative bile acid transporters. Impaired bile acid transport at the sinusoidal and canalicular membrane domains by these and other mediators of the inflammatory response may account for sepsis-associated cholestasis. 

Received 4 May 1995; accepted in final form 10 January 1996.
APS Manuscript Number G185-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 29 January 96