Hepatic uptake

Many compounds are efficiently taken up into hepatocytes in a Na+-dependent and -independent manner, and the effect of various inhibitors on the uptake of substrates is different depending on substrates. Now, so many transporters have been identified in the basolateral membrane of hepatocytes such as NTCP (Na+-taurocholate cotransporting polypeptide), OATPs, and OATs (organic anion transporters) 

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Klaassen, C. D., Watkins, J. B. (1984). Mechanisms of bile formation, hepatic uptake, and biliary excretion. Pharmacol. Rev. 36, 1-67. 

Roerdink, F., Dijkstra, J., Hartman, G., Bolscher, B., and Scher-phof, G. L. (1981). The involvement of parenchymal, Kupffer and endothelial liver cells in the hepatic uptake of intravenously injected liposomes, Biochim. Biophys. Acta, 677, 79-89. 

K Umezawa, A Karino, M Hayashi, K Tahara, A Kimura, S Awaza. Hepatic uptake of lipid-soluble drugs from fat emulsion. J Pharmacobio-Dynam 14 591-598, 1991. 

Ismair, M. G., et al. Hepatic uptake of cholecystokinin octapeptide by organic anion-transporting polypeptides OATP4 and OATP8 of rat and human liver. Gastroenterology 2001, 121, 1185-1190. 

Cui, Y., et al. Hepatic uptake of bilirubin and its conjugates by the human organic anion transporter SLC21A6J. Biol. Chem. 2001, 276, 9626-9630. 

The liver plays an important role in determining the oral bioavailability of drags. Drag molecules absorbed into the portal vein are taken up by hepatocytes, and then metabolized and/or excreted into the bile. For hydrophilic drugs, transporters located on the sinusoidal membrane are responsible for the hepatic uptake [1, 2]. Biliary excretion of many drags is also mediated by the primary active transporters, referred to as ATP-binding cassette transmembrane (ABC) transporters, located on the bile canalicular membrane [1, 3-5], Recently, many molecular biological... 

Transporter Molecules Responsible lor Hepatic Uptake of Organic Anions... 

Recently, molecular biology studies have been carried out on hepatic uptake transporters. With regard to the Na+-dependent hepatic uptake of bile acids, Na+-taurocholate cotransporting polypeptide (Ntcp/NTCP) has been cloned from both rodents and humans [14-17]. Ntcp/NTCP accepts bile salts, such as taurocholate and glycocholate, as well as some anionic compounds such as dehydroepian-drosterone sulfate and bromosulfophthalein [16, 18]. However, the presence of unidentified Na+-dependent transporters for anionic drugs (e.g., bumetanide) has also been suggested [19, 20]. 

In addition to OATP/Oatp family proteins, some of the organic anion transporter (OAT) family proteins may be responsible for hepatic uptake. Although many OAT family proteins are expressed in the kidney [36], human and rat OAT2 is also expressed in the liver [37, 38]. Human OAT2 transports p-amino-... 

Miyauchi, S., Sawada, Y., Iga, T., Hanano, M., Sugiyama, Y., Comparison of the hepatic uptake clearances of fifteen drugs with a wide range of membrane permeabilities in isolated rat hepatocytes and perfused rat livers, Pharm. Res. 1993, 10, 434-440. 

Reduced hepatic uptake and intestinal excretion of organic cations in mice with a targeted disruption of the organic cation transporter 1 (Octl [Slc22al]) gene, Mol. Cell. Biol. 2001, 23, 5471-5477. 

Gregoriadis, G., and Neerunjun, D.E., Control of the rate of hepatic uptake and catabolism of liposome-entrapped proteins injected into rats possible therapeutic applications, European Journal of Biochemistry, 1974, 47, 179-185. 

G7. Glass, G. B. J., Intestinal absorption and hepatic uptake of vitamin B12 in diseases of the gastrointestinal tract. Gastroenterology 30, 37 (1956). 

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