Developmental changes of the alpha-1-adrenergic receptor system in rat liver.
The alpha-1-adrenergic receptor system in liver plasma membranes purified from rats of different ages were quantified by means of the [3H]prazosin binding assay. Maximum binding was found to increase with age. The binding constant, however, does not change significantly. Coupling of the receptor to the nucleotide-binding protein was studied by competitive displacement analysis of [3H]prazosin binding with norepinephrine (NE) in the presence and in the absence of guanyl-5'-yl-imidodiphosphate (GppNHp). GppNHp induced a shift in the NE-displacement curves to lower affinities in membranes of adult rat livers, but not in liver membranes prepared from 12-day-old rats. Computer analysis showed that in the adult liver the displacement curves fit a two site binding model in the absence of GppNHp and in its presence a one site model. In liver membranes of adult rats more than 70% of the alpha-1-receptor population are apparently in the high affinity form, whereas in 12-days old rats the percentage is only 30%. Protease inhibitors were found without effect on the displacement curves. The phorbol ester 4 beta-phorbol 12-myristate 13-acetate (PMA) blocks the stimulation of glycogenolysis by alpha-1-agonists in hepatocytes of adult rats without changing their binding capacity for [3H]prazosin. The liver of newborn rats strongly responds towards exogenous stimulation by alpha-1-agonists.
Lange
R
R
Institute of Biochemistry, Karl-Marx University, Leipzig, German Democratic Republic.
Hermsdorf
T
T
Dettmer
D
D
Hofmann
E
E
D000375:Aging / Q000502:physiology; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D005943:Gluconeogenesis / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D011224:Prazosin; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D001786:Blood Glucose; D011942:Receptors, Adrenergic, alpha; D006165:Guanylyl Imidodiphosphate; D000001:Calcimycin; D011493:Protein Kinase C; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate; D009638:Norepinephrine; D011224:Prazosin