Regulation of organic anion and drug transporters of the sinusoidal membrane

Abstract

T” LIVER plays a key role in the clearance and metabolism of endogenous and xenobiotic lipophilic organic substances. Following uptake into the liver cell, these compounds undergo biotransformation and are subsequently eliminated from the hepatocyte via secretion into the bile canaliculus. Bile formation is driven primarily by the vectorial secretion of bile acids from sinusoidal blood into bile. Numerous transport systems have been identified on the functional and the molecular level which are involved in the basolateral uptake and the canalicular secretion of amphipathic organic substrates across the hepatocyte membrane (Fig. 1). The regulative pathways which modulate the expression and function of the multiple transport systems have been partially elucidated, in particular with respect to alterations of transport protein expression in cholestatic liver disease (l-3). Several studies have focussed on the effects of cholestasis on hepatic membrane transport processes, both in experimental rat models and in human cholestatic liver disease. The aim of this review is to summarize the most recent developments concerning the function and regulation of basolateral (sinusoidal) transport proteins involved in the uptake of organic anions and cations into the hepatocyte (Table 1).