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.