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

Gastroenterology. 2001 Nov;121(5):1185-90. doi: 10.1053/gast.2001.28704.


Background & aims: Cholecystokinin (CCK) is a major gastrointestinal peptide hormone that is released postprandially from the small intestine and exerts marked effects on gallbladder and gastrointestinal motility. The smaller isoforms CCK-8 and CCK-4 are rapidly taken up into hepatocytes, metabolized, and excreted into bile. Our aim was to identify and characterize the hepatocellular CCK-8 uptake system.

Methods: CCK-8 uptake was measured in Xenopus laevis oocytes expressing the organic anion-transporting polypeptides of rat liver (Oatp1, Oatp2, Oatp3, or Oatp4) and of human liver (OATP-A, OATP-B, OATP-C, or OATP8) and in primary cultured rat hepatocytes.

Results: Rat Oatp4 and human OATP8 efficiently mediated CCK-8 uptake in oocytes, with Michaelis constant (Km) values of 14.9 +/- 2.9 micromol/L and 11.1 +/- 2.9 micromol/L, respectively. CCK-8 uptake by hepatocytes was also saturable, with a Km of 6.7 +/- 2.1 micromol/L. The Km value in rat hepatocytes is consistent with Oatp4-mediated transport.

Conclusions: CCK-8 is selectively transported by rat Oatp4 and human OATP8, both of which are exclusively expressed at the basolateral membrane of hepatocytes. These 2 transporters are the first and probably the predominant hepatic uptake systems for CCK-8 and may be critical for the rapid clearance of this hormone from the circulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Hepatocytes / metabolism
  • Humans
  • Liver / metabolism*
  • Male
  • Organic Anion Transporters / physiology*
  • Organic Anion Transporters, Sodium-Independent / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Sincalide / pharmacokinetics*
  • Solute Carrier Organic Anion Transporter Family Member 1B3
  • Xenopus laevis


  • Organic Anion Transporters
  • Organic Anion Transporters, Sodium-Independent
  • SLCO1B3 protein, human
  • Solute Carrier Organic Anion Transporter Family Member 1B3
  • Sincalide