Molecular aspects of hepatobiliary transport.
M[umlaut]uller, Michael, and Peter L. M. Jansen.
Division of Gastroenterology and Hepatology, Department of
Medicine, University Hospital Groningen, 9700 RB Groningen, The
Netherlands
APStracts 3:0265G, 1996.
Generation of bile flow is a regulated, ATP-dependent process and
depends on the coordinated action of a number of transporter proteins
in the sinusoidal and canalicular domains of the hepatocyte.
Dysfunction of any of these proteins leads to retention of substrates
with conjugated hyperbilirubinemia or cholestasis as a result. In
recent years many of the transport proteins involved in bile
formation have been identified, cloned and functionally
characterized. The hepatocyte sinusoidal membrane contains transport
proteins for the hepatic uptake of organic anions and cations and for
the uptake of bile acids. The multispecific transport protein OATP
not only mediates the hepatic uptake of organic anions but of a
variety of organic amphiphilic compounds including organic cations.
OCT1 more specifically transports small organic cations. NTCP is the
sodium bile acid cotransporting protein which mediates the hepatic
uptake of bile acids. The canalicular transport proteins are able to
transport endogenous and exogenous metabolites into the bile against
steep concentration gradients. Most of these transporters are members
of the large ATP-binding cassette (ABC) superfamily and their
transport function directly depend on the hydrolysis of Mg++/ATP. At
least five ABC-transporter proteins have been characterized sofar:
(I) MDR1 mediates excretion of hydrophobic mostly cationic
metabolites; (II) MDR3 is involved in phosphatidylcholine secretion;
(III) cBAT mediates secretion of monovalent bile salts and provides
the molecular basis of bile acid dependent bile flow; (IV) SPGP is
exclusively expressed in the liver but its function is currently
unknown; (V) MRP2 mediates the excretion of multivalent anionic
conjugates.
Received 17 December 1996; accepted in final form 17 December
1996.
APS Manuscript Number G501-6.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996