Simultaneous loss and reappearance of α₁-adrenergic responses and [³H]prazosin binding sites in rat liver after irreversible blockade by phenoxybenzamine

The relative influences of the in vivo administration of phenoxybenzamine on in vitro binding to α1-adrenergic receptors and α1-receptor-mediated responses were studied. Phenoxybenzamine treatment reduced maximal specific binding of the α1-selective antagonist [3H]prazosin to liver cell membranes. This response was rapid (< 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, α1-binding and both of the α1-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 α1-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.