Processing of cholecystokinin by isolated liver cells

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Abstract

Although hepatic uptake of cholecystokinin (CCK) has been demonstrated, the liver cell involved and the mechanism of uptake remain unclear. We have used dispersed rat hepatocytes, Kupffer cells, and hepatic endothelial cells to characterize uptake and metabolism of radiolabeled CCK peptides. Only rat hepatocytes showed significant uptake of 125I-labeled cholecystokinin octapeptide (125I-CCK-8). Peptide specificity of uptake by hepatocytes was similar to that seen in the isolated perfused rat liver, with extraction of 125I-CCK-8 being sevenfold greater than that of 125I-CCK-33. Uptake was saturable, as 10-4 M CCK-4 inhibited uptake of 125I-CCK-8 by 85%. Uptake was rapid, temperature dependent, and extensive and was decreased by metabolic inhibition, a proteolytic enzyme (trypsin), organic anions (sulfobromophthalein and taurocholic acid), and an inhibitor of anion transport 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid. In addition, uptake was dependent on extracellular anions but not on extracellular sodium, calcium, or magnesium. After uptake, hepatocytes released radiolabel in a time- and temperature-dependent manner, predominantly in metabolized forms. Thus the hepatocyte is the liver cell that extracts CCK by an active, anion-dependent process. The characteristics of the uptake process resemble those described for organic anions and small, cyclic peptides and suggest that small, linear peptides may undergo hepatocyte extraction by a similar mechanism.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume257
Issue number2
StatePublished - 1989

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Cholecystokinin
Hepatocytes
Anions
Liver
Peptides
Tetragastrin
Sulfobromophthalein
4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid
Liver Extracts
Sincalide
Cyclic Peptides
Taurocholic Acid
Temperature
Kupffer Cells
Cell Extracts
Trypsin
Magnesium
Peptide Hydrolases
Endothelial Cells
Sodium

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology

Cite this

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title = "Processing of cholecystokinin by isolated liver cells",
abstract = "Although hepatic uptake of cholecystokinin (CCK) has been demonstrated, the liver cell involved and the mechanism of uptake remain unclear. We have used dispersed rat hepatocytes, Kupffer cells, and hepatic endothelial cells to characterize uptake and metabolism of radiolabeled CCK peptides. Only rat hepatocytes showed significant uptake of 125I-labeled cholecystokinin octapeptide (125I-CCK-8). Peptide specificity of uptake by hepatocytes was similar to that seen in the isolated perfused rat liver, with extraction of 125I-CCK-8 being sevenfold greater than that of 125I-CCK-33. Uptake was saturable, as 10-4 M CCK-4 inhibited uptake of 125I-CCK-8 by 85{\%}. Uptake was rapid, temperature dependent, and extensive and was decreased by metabolic inhibition, a proteolytic enzyme (trypsin), organic anions (sulfobromophthalein and taurocholic acid), and an inhibitor of anion transport 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid. In addition, uptake was dependent on extracellular anions but not on extracellular sodium, calcium, or magnesium. After uptake, hepatocytes released radiolabel in a time- and temperature-dependent manner, predominantly in metabolized forms. Thus the hepatocyte is the liver cell that extracts CCK by an active, anion-dependent process. The characteristics of the uptake process resemble those described for organic anions and small, cyclic peptides and suggest that small, linear peptides may undergo hepatocyte extraction by a similar mechanism.",
author = "Gores, {Gregory James} and Kost, {L. J.} and Miller, {Laurence J} and {La Russo}, {Nicholas F}",
year = "1989",
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journal = "American Journal of Physiology - Renal Fluid and Electrolyte Physiology",
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T1 - Processing of cholecystokinin by isolated liver cells

AU - Gores, Gregory James

AU - Kost, L. J.

AU - Miller, Laurence J

AU - La Russo, Nicholas F

PY - 1989

Y1 - 1989

N2 - Although hepatic uptake of cholecystokinin (CCK) has been demonstrated, the liver cell involved and the mechanism of uptake remain unclear. We have used dispersed rat hepatocytes, Kupffer cells, and hepatic endothelial cells to characterize uptake and metabolism of radiolabeled CCK peptides. Only rat hepatocytes showed significant uptake of 125I-labeled cholecystokinin octapeptide (125I-CCK-8). Peptide specificity of uptake by hepatocytes was similar to that seen in the isolated perfused rat liver, with extraction of 125I-CCK-8 being sevenfold greater than that of 125I-CCK-33. Uptake was saturable, as 10-4 M CCK-4 inhibited uptake of 125I-CCK-8 by 85%. Uptake was rapid, temperature dependent, and extensive and was decreased by metabolic inhibition, a proteolytic enzyme (trypsin), organic anions (sulfobromophthalein and taurocholic acid), and an inhibitor of anion transport 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid. In addition, uptake was dependent on extracellular anions but not on extracellular sodium, calcium, or magnesium. After uptake, hepatocytes released radiolabel in a time- and temperature-dependent manner, predominantly in metabolized forms. Thus the hepatocyte is the liver cell that extracts CCK by an active, anion-dependent process. The characteristics of the uptake process resemble those described for organic anions and small, cyclic peptides and suggest that small, linear peptides may undergo hepatocyte extraction by a similar mechanism.

AB - Although hepatic uptake of cholecystokinin (CCK) has been demonstrated, the liver cell involved and the mechanism of uptake remain unclear. We have used dispersed rat hepatocytes, Kupffer cells, and hepatic endothelial cells to characterize uptake and metabolism of radiolabeled CCK peptides. Only rat hepatocytes showed significant uptake of 125I-labeled cholecystokinin octapeptide (125I-CCK-8). Peptide specificity of uptake by hepatocytes was similar to that seen in the isolated perfused rat liver, with extraction of 125I-CCK-8 being sevenfold greater than that of 125I-CCK-33. Uptake was saturable, as 10-4 M CCK-4 inhibited uptake of 125I-CCK-8 by 85%. Uptake was rapid, temperature dependent, and extensive and was decreased by metabolic inhibition, a proteolytic enzyme (trypsin), organic anions (sulfobromophthalein and taurocholic acid), and an inhibitor of anion transport 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid. In addition, uptake was dependent on extracellular anions but not on extracellular sodium, calcium, or magnesium. After uptake, hepatocytes released radiolabel in a time- and temperature-dependent manner, predominantly in metabolized forms. Thus the hepatocyte is the liver cell that extracts CCK by an active, anion-dependent process. The characteristics of the uptake process resemble those described for organic anions and small, cyclic peptides and suggest that small, linear peptides may undergo hepatocyte extraction by a similar mechanism.

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