Catecholamine-induced subsensitivity of adenylate cyclase associated with loss of beta-adrenergic receptor binding sites

Proc Natl Acad Sci U S A. 1975 May;72(5):1945-9. doi: 10.1073/pnas.72.5.1945.


Injection of frogs with beta-adrenergic catecholamines for 1-24 hr produces marked subsensitivity of the erythrocyte membrane adenylate cyclase [ATP pyrophosphate-lyase (cyclizing); EC] to in vitro stimulation by isoproterenol. The subsensitization is specific for catecholamine stimulation, since basal and fluoride-stimulated enzyme activity are unaffected. Maximum isoproterenol-stimulated adenylate cyclase activity declines by 75% in the isoproterenol-treated animals (P less than 0.001). The concentration of isoproterenol causing one-half maximal activation of adenylate cyclase, however, is unaltered. (-)[3H]Alprenolol, a potent competitive beta-adrenergic antagonist, was used to study directly the beta-adrenergic receptor binding sites in the erythrocyte membranes from control and subsensitized animals. A highly significant (P less than 0.005) 60% fall in the number of the beta-adrenergic receptor binding sites ("specific"(-)[3H]alprenolol binding sites) in the treated animals was found. The binding affinity of the sites was not markedly altered. These data suggest that beta-adrenergic catecholamines are able to regulate catecholamine sensitivity of tissues in vivo, by regulating the properties of the beta-adrenergic receptor binding sites.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenylyl Cyclases / blood*
  • Alprenolol / pharmacology*
  • Animals
  • Anura
  • Binding Sites
  • Catecholamines / pharmacology*
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Epinephrine / pharmacology
  • Erythrocytes / drug effects
  • Erythrocytes / enzymology*
  • Fluorides / pharmacology
  • Isoproterenol / pharmacology
  • Kinetics
  • Norepinephrine / pharmacology
  • Phenoxybenzamine / pharmacology
  • Phentolamine / pharmacology
  • Propranolol / pharmacology
  • Receptors, Adrenergic*
  • Stereoisomerism


  • Catecholamines
  • Receptors, Adrenergic
  • Phenoxybenzamine
  • Alprenolol
  • Propranolol
  • Adenylyl Cyclases
  • Isoproterenol
  • Fluorides
  • Norepinephrine
  • Epinephrine
  • Phentolamine