Chemical-induced interference with hepatocellular transport. Role in cholestasis

Abstract

Transport of endogenous chemicals both into (at the basolateral membrane) and out of (at the canalicular membrane) hepatocytes plays an important role in bile formation. Hence, interference with these processes, for example by chemicals, may result in reduced bile output. Several different systems are available for the study of transport and hence chemicals that may interfere with the process. These have been used to varying degrees with isolated hepatocytes probably being the most popular over recent years. It is likely that hepatocyte couplets and highly purified plasma membrane vesicles will be increasingly employed over the ensuing years. The inhibitory effects of several chemicals on the transport of bile acids have been demonstrated with indications that this may help to account for some aspects of chemical-induced hepatobiliary dysfunction. For example, the inhibition of transport of bile acids by cyclosporin A is consistent with the reported pattern of liver dysfunction in patients on high doses of this immunosuppressant. Investigation into chemical-induced interference with electrolyte transport has yet to receive the same degree of attention. This and other aspects have been suggested as deserving of and likely to be subjected to more intensive experimentation over the next few years.