title: Simultaneous loss and reappearance of alpha 1-adrenergic responses and [3H]prazosin binding sites in rat liver after irreversible blockade by phenoxybenzamine.
abstract: The relative influences of the in vivo administration of phenoxybenzamine on in vitro binding to alpha 1-adrenergic receptors and alpha 1-receptor-mediated responses were studied. Phenoxybenzamine treatment reduced maximal specific binding of the alpha 1-selective antagonist [3H]prazosin to liver cell membranes. This response was rapid (less than 90 min) and half-maximal following a phenoxybenzamine dose of approx. 10 mg/kg. A similar decrease in the ability of phenylephrine to stimulate glucose release and 45Ca2+ efflux from liver slices was also noted after phenoxybenzamine treatment. During the recovery period following administration of 30 mg/kg phenoxybenzamine, [3H]prazosin specific binding and phenylephrine-stimulated glucose release and 45Ca2+ efflux returned to their respective control levels with t 1/2 values of 42, 49 and 38 h, respectively. At all times studied during the recovery period, alpha 1-binding and both of the alpha 1-responses were similar fractions of their respective control values. These observations indicate that a close relationship exists between the density of [3H]prazosin binding sites and the ability of rat liver to respond to alpha 1-stimulation. We suggest that the binding sites identified in studies using the antagonist [3H]prazosin and those through which the agonist phenylephrine stimulates glucose release and 45Ca2+ efflux are either identical or in equilibrium with each other.
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D010643:Phenoxybenzamine / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000378:metabolism*; D011799:Quinazolines / Q000378:metabolism*; D051381:Rats; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*
chemical_list: D011799:Quinazolines; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D010643:Phenoxybenzamine; D010656:Phenylephrine; D005947:Glucose; D002118:Calcium; D011224:Prazosin