Age-related changes in the adrenergic control of glycogenolysis in rat liver: the significance of changes in receptor density.
The present study examined the developmental changes in the adrenergic control of glycogenolysis in the rat model. A relatively new beta-adrenergic radioligand, 125I-iodocyanopindolol (ICP), was examined in binding assays with rat liver plasma membrane (LPM). ICP demonstrated both a higher specificity and a greater affinity for beta-adrenergic receptors than any previously available beta-adrenergic radioligand used to study rat LPM. Utilizing this new ligand it was found that beta-adrenergic receptor density decreased from 114 +/- 4 fmol mg-1 in newborn LPM to 19 +/- 3 fmol mg-1 in adult male LPM. In contrast alpha-adrenergic receptor density examined using 3H-prazosin increased from 161 +/- 14 fmol mg-1 in the newborn to 554 +/- 59 fmol mg-1 in the adult male. The results of ICP displacement assays employing various beta-adrenergic agonists and antagonists indicated that ICP binding sites were beta 2-adrenergic receptors. Both guanosine triphosphate and its nonhydrolyzable synthetic analog guanylyl-imidodiphosphate lowered the affinity of epinephrine for ICP binding sites similarly in newborn and adult LPM. Thus the coupling of receptor to guanine nucleotide regulatory protein appeared to be the same in both age groups examined. In isolated hepatocytes glycogen phosphorylase activation was mediated by beta 2-adrenergic stimuli in the newborn and predominantly alpha-adrenergic stimuli in the adult male. These results suggest that the change in glycogen phosphorylase activation from beta- to predominantly alpha-adrenergic mechanisms seen with maturation is related to changes in receptor density.
Bendeck
J L
JL
Noguchi
A
A
D000375:Aging; D000818:Animals; D002462:Cell Membrane; D005947:Glucose / Q000502:physiology*; D007457:Iodine Radioisotopes; D020120:Iodocyanopindolol; D008099:Liver / Q000648:ultrastructure; D008112:Liver Glycogen / Q000378:metabolism*; D008297:Male; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D011485:Protein Binding; D051381:Rats / Q000502:physiology*; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
D007457:Iodine Radioisotopes; D008112:Liver Glycogen; D011943:Receptors, Adrenergic, beta; D020120:Iodocyanopindolol; D010869:Pindolol; D005947:Glucose