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

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Abstract

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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume250
Issue number3
StatePublished - 1986

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Cholecystokinin
Peptides
Liver
Tetragastrin
Sincalide
Taurocholic Acid
Wheat Germ Agglutinins
cholecystokinin 8
Concanavalin A
Bile Acids and Salts
Lectins
Sulfates
Tyrosine
Esters

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology

Cite this

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title = "Hepatic processing of cholecystokinin peptides. I. Structural specificity and mechanism of hepatic extraction",
abstract = "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.",
author = "Gores, {Gregory James} and {La Russo}, {Nicholas F} and Miller, {Laurence J}",
year = "1986",
language = "English (US)",
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T1 - Hepatic processing of cholecystokinin peptides. I. Structural specificity and mechanism of hepatic extraction

AU - Gores, Gregory James

AU - La Russo, Nicholas F

AU - Miller, Laurence J

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