VOL. 2, No. 3, July 2005

J. J. G. Marin, et al. [2005] Med Hypotheses Res 2: 425-448.

Emerging Interest in Bile Acid Transporters in
Pathophysiology and Pharmacology

Jose J. G. Marin*, Marta R. Romero, Marta Vallejo, Maria J. Perez
and Oscar Briz

Laboratory of Experimental Hepatology and Drug Targeting, Department of Physiology and
Pharmacology (J.J.G.M., O.B.), Department of Biochemistry and Molecular Biology
(M.R.R., M.V.), Research Unit, University Hospital (M.J.P.), University of Salamanca, 37007
Salamanca, Spain

Abstract. Bile acids form a large family of compounds with marked organotropic
characteristics. These allow them to be kept within the enterohepatic circulation, which
includes the liver, biliary system, intestine and portal vein. This circuit is based on the
existence of plasma membrane proteins able to efficiently transport bile acids from the
sinusoidal blood into bile and from the intestinal lumen to the portal blood. The carriers
involved in bile acid transport belong to different protein families (SLC10A, SLCO, ABCB,
ABCC, and ABCG). The energy driving such transport varies from substrate gradient to
sodium-cotransport, anion-exchange or ATP-hydrolysis. The abnormal functioning of some
of these transporters accounts for diseases such as cholestasis or intestinal malabsorption,
whereas impaired hepatobiliary function, resulting in bile acid accumulation, induces
changes in the expression and/or sorting of these proteins. Owing to the broad substrate
specificity of some of these transporters they have been implicated in several interactions
between drugs, toxins, food components and endogenous substances. In addition to other
pharmacological and pharmaceutical uses of bile acids, their organotropism has resulted in a
large list of compounds that have been conjugated with them. The benefits of these drugs
include their ability to target pharmacologically active agents toward the liver, the biliary
system and the intestine. Moreover, pharmacological modulation of the expression/function
of some of these transporters is of great importance. Thus, cholesterol-lowering drugs able to
interact with bile acid transporters, inhibit enterohepatic circulation of bile acids, hence
increasing fecal elimination and stimulating cholesterol metabolism, have been developed.

*Address all correspondence to: Dr. Jose J.G. Marin, Department of Physiology and
Pharmacology, Campus Miguel de Unamuno, E.D. S-09, 37007-Salamanca, Spain.
Phone: 34 923 294674; Fax: 34 923 294669; E-mail:

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