Hepatic uptake of cholecystokinin octapeptide by organic anion-transporting polypeptides OATP4 and OATP8 of rat and human liver

摘要: BACKGROUND & AIMS: Cholecystokinin (CCK) is a major gastrointestinal peptide hormone that released postprandially from the small intestine and exerts marked effects on gallbladder motility. The smaller isoforms CCK-8 CCK-4 are rapidly taken up into hepatocytes, metabolized, excreted bile. Our aim was to identify characterize hepatocellular uptake system. METHODS: measured in Xenopus laevis oocytes expressing organic anion-transporting polypeptides of rat liver (Oatp1, Oatp2, Oatp3, or Oatp4) human (OATP-A, OATP-B, OATP-C, OATP8) primary cultured hepatocytes. RESULTS: Rat Oatp4 OATP8 efficiently mediated oocytes, with Michaelis constant (Km) values 14.9 +/- 2.9 micromol/L 11.1 micromol/L, respectively. by hepatocytes also saturable, Km 6.7 2.1 micromol/L. value consistent Oatp4-mediated transport. CONCLUSIONS: selectively transported OATP8, both which exclusively expressed at basolateral membrane These 2 transporters first probably predominant hepatic systems for may be critical rapid clearance this circulation.