125I-IODOCYANOPINDOLOL (ICP) BINDING TO NEWBORN RAT LIVER MEMBRANE

Abstract

Rat liver glycogenolysis is stimulated by β-adrenergic mechanism in newborn (NB) but a in adult (AD). It has been speculated that this maturational change from β to α control is related to changes in numbers of plasma membrane (PM) receptors. However direct binding of β radioligands to NB liver had been unsuccessful. We examined a new β ligand ICP in binding assays with NB and AD liver PM and correlated with adrenergic stimulation of glycogen phosphorylase (GP) in isolated hepatocytes. PM was purified 7±1 times in NB and 11±2 times in AD assessed by 5'-nucleotidase. ICP binding was saturable, reversible and was displaced by Isop>Epi>Norepi and Alprenolol>>Metoprolol in both NB and AD. GTP lowered the Epi affinity of ICP binding sites similarly at both ages. The number of ICP (β) binding sites was contrasted with α1 - ligand, 3H-Prazosin binding sites.GP was also stimulated by Isop>Epi>Norepi in NB hepatocytes. Inhibition of Epi stimulated GP was Alprenolol (A)>>Phentolamine (P) in NB and P>>A in AD. We conclude 1) liver ICP binding sites are β2 subtype receptors and 2) the change in GP stimulation from β to α mechanism seen with maturation is related to changes in receptor number.