Hepatic processing of cholecystokinin peptides. I. Structural specificity and mechanism of hepatic extraction.
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.
D000818:Animals; D002766:Cholecystokinin / Q000378:metabolism*; D007457:Iodine Radioisotopes; D008099:Liver / Q000378:metabolism*; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D012844:Sincalide / Q000031:analogs & derivatives / Q000378:metabolism*; D013329:Structure-Activity Relationship
D007457:Iodine Radioisotopes; D010446:Peptide Fragments; C044201:cholecystokinin (26-33); D002766:Cholecystokinin; D012844:Sincalide