Lack of metabolic effects of cholecystokinin on hepatocytes

Louis J. Kost, Gregory James Gores, John M. Sayles, Laurence J Miller, John J. Lemasters, Brian Herman, Nicholas F La Russo

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

We previously reported that the liver was the major organ that extracts small, biologically active, circulating forms of cholecystokinin. Although our work indicated extensive degradation of cholecystokinin extracted from plasma during its transit across the hepatocyte, it was unclear whether cholecystokinin night also have a physiological effect on this cell before its intracellular degradation. Therefore we tested the hypothesis that cholecystokinin has a direct biological effect on hepatocytes. Using freshly isolated or cultured hepatocytes, we studied whether cholecystokinin-octapeptide alters protein synthesis, affects amino acid transport or influences cytosolic free calcium concentrations. Using liver slices, we also determined the effect of cholecystokinin-octapeptide on cyclic nucleotide levels. Cholecystokininoctapeptide, up to a concentration of 1 μmol/L, had no effect on the incorporation of radiolabeled amino acids into total hepatocyte protein; in contrast, comparable molar amounts of insulin stimulated protein synthesis by as much as 37% (ED50 = 1.5 × 10-10 mol/L). Although insulin and glucagon stimulated the transport into hepatocytes of 14C-α-aminoisobutyric acid, a nonmetabolizable amino acid analog, cholecystokinin-octapeptide had no effect. Cholecystokinin-octapeptide also did not affect either the concentration of calcium in individual hepatocytes, as measured by digitized video microscopy using Fura-2, or the levels of cyclic AMP or cyclic GMP in liver slices. Our results show that cholecystokinin has no effect on protein synthesis, on amino acid transport or on hepatocyte calcium and cyclic nucleotide levels. These and our previous data suggest that the primary outcome of hepatic extraction of cholecystokinin is hormone degradation.

Original languageEnglish (US)
Pages (from-to)301-305
Number of pages5
JournalHepatology
Volume12
Issue number2
StatePublished - Aug 1990

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Cholecystokinin
Hepatocytes
Sincalide
Amino Acids
Liver
Cyclic Nucleotides
Calcium
Proteins
Insulin
Aminoisobutyric Acids
Video Microscopy
Fura-2
Cyclic GMP
Glucagon
Cyclic AMP
Hormones

ASJC Scopus subject areas

  • Hepatology

Cite this

Kost, L. J., Gores, G. J., Sayles, J. M., Miller, L. J., Lemasters, J. J., Herman, B., & La Russo, N. F. (1990). Lack of metabolic effects of cholecystokinin on hepatocytes. Hepatology, 12(2), 301-305.

Lack of metabolic effects of cholecystokinin on hepatocytes. / Kost, Louis J.; Gores, Gregory James; Sayles, John M.; Miller, Laurence J; Lemasters, John J.; Herman, Brian; La Russo, Nicholas F.

In: Hepatology, Vol. 12, No. 2, 08.1990, p. 301-305.

Research output: Contribution to journalArticle

Kost, LJ, Gores, GJ, Sayles, JM, Miller, LJ, Lemasters, JJ, Herman, B & La Russo, NF 1990, 'Lack of metabolic effects of cholecystokinin on hepatocytes', Hepatology, vol. 12, no. 2, pp. 301-305.
Kost LJ, Gores GJ, Sayles JM, Miller LJ, Lemasters JJ, Herman B et al. Lack of metabolic effects of cholecystokinin on hepatocytes. Hepatology. 1990 Aug;12(2):301-305.
Kost, Louis J. ; Gores, Gregory James ; Sayles, John M. ; Miller, Laurence J ; Lemasters, John J. ; Herman, Brian ; La Russo, Nicholas F. / Lack of metabolic effects of cholecystokinin on hepatocytes. In: Hepatology. 1990 ; Vol. 12, No. 2. pp. 301-305.
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