Simultaneous loss and reappearance of alpha 1-adrenergic responses and [3H]prazosin binding sites in rat liver after irreversible blockade by phenoxybenzamine

Biochim Biophys Acta. 1983 May 25;757(2):156-63. doi: 10.1016/0304-4165(83)90103-4.


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

  • Animals
  • Calcium / metabolism
  • Female
  • Glucose / metabolism
  • Kinetics
  • Liver / drug effects
  • Liver / metabolism*
  • Phenoxybenzamine / pharmacology*
  • Phenylephrine / pharmacology
  • Prazosin / metabolism*
  • Quinazolines / metabolism*
  • Rats
  • Receptors, Adrenergic / metabolism*
  • Receptors, Adrenergic, alpha / metabolism*


  • Quinazolines
  • Receptors, Adrenergic
  • Receptors, Adrenergic, alpha
  • Phenoxybenzamine
  • Phenylephrine
  • Glucose
  • Calcium
  • Prazosin