AJP - Gastrointestinal and Liver Physiology, Vol 250, Issue 3 344-G349, Copyright © 1986 by American Physiological Society

ARTICLES

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

G. J. Gores, N. F. LaRusso and L. J. Miller

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.

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				S. Eisen, R. J. Phillips, N. Geary, E. A. Baronowsky, T. L. Powley, and G. P. Smith Inhibitory effects on intake of cholecystokinin-8 and cholecystokinin-33 in rats with hepatic proper or common hepatic branch vagal innervation Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2005; 289(2): R456 - R462. [Abstract] [Full Text] [PDF]