A quantitative analysis of glucagon binding to isolated intact neonatal and adult rat hepatocytes on the basis of two different binding models.
The interaction of glucagon with specific receptors has been studied in isolated intact neonatal and adult rat hepatocytes. The hormone binding measured directly with 125I-labelled glucagon was saturable and reversible. The 125I-labelled glucagon binding was inhibited by unlabelled homologous hormone at concentrations ranging from 0.5 nM to 50 microM. Two different binding models were assumed to analyse the binding data by a nonlinear least-squares procedure: (I) a single class of independent sites and (II) two classes of independent sites. The comparison of the fitted theoretical curves reveals that both binding models are in fact compatible with these data. Adult hepatocytes have a considerably higher affinity for glucagon than neonatal hepatocytes; the binding capacity of neonatal liver cells from 1-7-days-old rats proved to be markedly reduced compared with the cells from adult rats. The glucagon-induced intracellular cyclic AMP production was measured at various hormone concentrations under conditions identical to those for the determination of extracellular hormone binding. The correlation of both parameters indicates a direct connection between receptor-occupancy and adenylate cyclase stimulation of both parameters indicates a direct connection between receptor-occupancy and adenylate cyclase stimulation. These results suggest that a decreased receptor concentration in neonatal hepatocytes is responsible for the decreased cyclic AMP production.
D000367:Age Factors; D000818:Animals; D003201:Computers; D000242:Cyclic AMP / Q000378:metabolism; D005934:Glucagon / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018027:Receptors, Glucagon; D013997:Time Factors
D011956:Receptors, Cell Surface; D018027:Receptors, Glucagon; D005934:Glucagon; D000242:Cyclic AMP