Hepatic processing of cholecystokinin peptides. I. Structural specificity and mechanism of hepatic extraction

Am J Physiol. 1986 Mar;250(3 Pt 1):G344-9. doi: 10.1152/ajpgi.1986.250.3.G344.


Since the liver is a target tissue of many biologically important molecules, we have studied the hepatic uptake of cholecystokinin (CCK) with the isolated, perfused rat liver and a series of radioiodinated and unlabeled CCK peptides. Of the naturally occurring forms of CCK, cholecystokinin octapeptide (CCK-8) was extensively extracted (26 +/- 0.7% of Bolton-Hunter-labeled CCK-8, 59% of unlabeled CCK-8) in a single pass through the liver, while CCK-33 was minimally extracted (3.1 +/- 1.2% of Bolton-Hunter-labeled CCK-33). Studies of structural specificity showed that the sulfate ester on the tyrosine residue of CCK-8 decreased its hepatic extraction, that the carboxyl-terminal tetrapeptide region of CCK-8 was more important for this uptake process than was the amino-terminal tetrapeptide region, and that oxidation reduced uptake of CCK. First-pass hepatic extraction of unlabeled CCK-8 was shown to be a high-capacity process; however, uptake of radioiodinated CCK-8 was partially saturable with unlabeled CCK-4. Specific lectins (wheat-germ agglutinin, concanavalin A) and a bile acid (taurocholate) inhibited hepatic extraction of CCK-8 in a concentration-dependent manner. These data are consistent with a highly specific cellular extraction process for CCK in the liver.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cholecystokinin / metabolism*
  • Iodine Radioisotopes
  • Liver / metabolism*
  • Male
  • Peptide Fragments / metabolism
  • Perfusion
  • Rats
  • Rats, Inbred Strains
  • Sincalide / analogs & derivatives
  • Sincalide / metabolism*
  • Structure-Activity Relationship


  • Iodine Radioisotopes
  • Peptide Fragments
  • cholecystokinin (26-33)
  • Cholecystokinin
  • Sincalide