Molecular mechanisms of hepatic bile salt transport from sinusoidal blood into bile. Meier, Peter J. Division of Clinical Pharmacology and Toxicology, Department of Medicine, University Hospital, CH-8091 Zuerich/Switzerland
APStracts 2:0180G, 1995.
An increasingly complex picture has emerged in recent years regarding the bile salt transport polarity of hepatocytes. At the sinusoidal (or basolateral) plasma membrane two bile salt transporting polypeptides have been cloned. The Na+-taurocholate cotransporting polypeptide (Ntcp) can account for most, if not all, physiologic properties of the Na+-dependent bile salt uptake function in mammalian hepatocytes. The cloned organic anion transporting protein (Oatp1) can mediate Na+-independent transport of bile salts, sulfobromophthalein, estrogenconjugates and of a variety of other amphipatic cholephilic compounds. Hence, Oatp1 appears to correspond to the previously suggested "multispecific bile salt transporter". - Intracellular bile salt transport can be mediated by different pathways. Under basal bile salt flux conditions, conjugated trihydroxy-bile salts bind to cytoplasmic binding proteins and reach the canalicular plasma membrane predominantly via cytoplasmic diffusion. More hydrophobic mono- and dihydroxy- and high concentrations of trihydroxy bile salts associate with intracellular membrane bound compartements including transcytotic vesicles, endoplasmic reticulum (ER) and Golgi complex. A facilitated bile salt diffusion pathway has been demonstrated in the ER. The exact role of these and other (e.g. lysosomes, "tubulovesicular structures") organelles in overall vectorial transport of bile salts across hepatocytes is not yet known. - Canalicular bile salt secretion is mediated by two ATP-dependent transport systems, one for monovalent bile salts and the second for divalent sulfated or glucuronidated bile salt conjugates. The latter is identical with the "multispecific organic anion transporter (MOAT)" that also transports other divalent organic anions such as for example glutathione-S-conjugates. Potential dependent canalicular bile salt secretion has also been suggested to occur, but its exact mechanism and physiologic significance remain unclear, since a potential driven bile salt uptake system has also been identified in the ER. Hypothetically, and similar to changes in cell volume, the intracellular potential could also play a role in the regulation of the number of bile salt carriers at the canalicular membrane and thereby indirectly influence the maximal canalicular bile salt transport capacity of hepatocytes. 

Received 21 April 1995; accepted in final form 15 August 1995.
APS Manuscript Number G365-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 September 1995.