Interactions of glucagon and glucagon analogs with isolated canine hepatocytes

W. A. Hagopian, H. S. Tager, B. Gysin, D. Trivedi, V. J. Hruby

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

We have used glucagon and nine glucagon analogs to investigate the interactions of these ligands with glucagon-binding sites present on isolated canine hepatocytes. Curves reflecting the inhibition of 125I-labeled glucagon or 125I-labeled analog binding to cells by the 10 peptides spanned, overall, a 106-fold range of hormone concentration, were consistent with hormone binding to two classes of binding sites in each case, and fell into two groups, one of which contained curves that were considerably more shallow than the other. Only conditions that emphasized prior binding to low affinity sites resulted in the rapid and extensive dissociation of receptor-bound ligand from isolated cells. Finally, all 10 peptides exhibited a concentration-dependent inhibition of the incorporation of [14C]fructose into hepatocyte glycogen that correlated best with dissociation constants for high affinity rather than for low affinity binding. We conclude that (a) the association of ligand with the high and low affinity glucagon-binding sites of isolated canine hepatocytes is a characteristic of analogs modified at diverse sites throughout the peptide hormone, (b) the different rates of dissociation of ligand from the two populations of binding sites most probably account for the biphasic dissociation of ligand from isolated cells and for the different affinities of the two receptor populations for ligand, and (c) the activity of glucagon and glucagon analogs to inhibit the incorporation of fructose into hepatocyte glycogen arises from the association of ligand with high affinity binding sites.

Original languageEnglish (US)
Pages (from-to)15506-15513
Number of pages8
JournalJournal of Biological Chemistry
Volume262
Issue number32
StatePublished - Jan 1 1987

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Hagopian, W. A., Tager, H. S., Gysin, B., Trivedi, D., & Hruby, V. J. (1987). Interactions of glucagon and glucagon analogs with isolated canine hepatocytes. Journal of Biological Chemistry, 262(32), 15506-15513.