Sinusoidal (basolateral) bile salt uptake systems of hepatocytes

Abstract

Sinusoidal (basolateral) bile sale uptake is mediated by Na(+)-dependent and Na(+)-independent transport systems. Two hepatocellular bile salt uptake systems have been cloned from rat and human livers. The Na(+)-taurocholate cotransporting polypeptides Ntcp and NTCP mediate strictly Na(+)-dependent bile salt uptake into rat and human hepatocytes, respectively. Extensive characterization of Ntcp expression and function in a variety of eukaryotic cell lines, cultured hepatocytes, and intact rat liver indicates that Ntcp can account for most, if not all, Na(+)-dependent bile salt transport functions in rat liver. Whether the same is also true for the human NTCP is less well understood. The Na(+)-independent organic anion transporting polypeptides oatpl (rat) and OATP (human) exhibit a wide and charge-independent substrate specificity. Their transported substrates include sulfobromophthalein, bile salts, estrone-3-sulfates, ouabain, and other neutral steroids, as well as certain amphipathic organic cations. Its broad and charge-independent substrate specificity indicates that oatpl represents the previously suggested hepatocellular "multispecific bile salt transporter.". Oatpl and OATP are also expressed in the kidney and brain. Whether there are additional oatpl- and OATP-related proteins involved in overall hepatic drug and steroid clearance remains to be determined.