AJP - Gastrointestinal and Liver Physiology, Vol 250, Issue 3 350-G356, Copyright © 1986 by American Physiological Society
Hepatic processing of cholecystokinin peptides. II. Cellular metabolism, transport, and biliary excretion
G. J. Gores, L. J. Miller and N. F. LaRusso
We have shown that radiolabeled cholecystokinin octapeptide (CCK-8),
CCK-8-desulfate, and CCK-4 are extracted by the liver in a structurally
specific manner. Thus, we studied the fate of the extracted radiolabeled
peptides by quantitating biliary excretion and determining the nature of
the metabolites in bile. There was rapid biliary excretion of labeled
CCK-8, CCK-8-desulfate, and CCK-4 by the isolated, perfused rat liver;
greater than 75% of the extracted dose and greater than 20% of the injected
dose appeared in bile within 20 min after a single pass across the liver.
By means of high-performance liquid chromatography and immunoprecipitation,
we showed that CCK-8-desulfate and CCK-4 appeared in bile in completely
metabolized forms. In contrast, for CCK-8, approximately 20% of the major
forms of the label in bile was intact labeled octapeptide. To gain insight
into the subcellular sites of metabolism and transhepatic transport of
CCK-8, we also determined the effects of taurocholate, lysosomotropic
agents, and microtubule binding agents on biliary excretion. Taurocholate
had no effect on the percentage of the extracted label excreted into bile.
Neither the percentage of the extracted label excreted into bile. Neither
lysosmotropic agent, leupeptin, nor chloroquine affected the percentage of
the extracted label or the nature of the metabolites appearing in bile. Two
microtubule binding agents, vinblastine and colchicine, also did not affect
the percentage of the extracted label appearing in bile.(ABSTRACT TRUNCATED
AT 250 WORDS)
