Interaction of beta-adrenergic receptors with the inhibitory guanine nucleotide-binding protein of adenylate cyclase in membranes prepared from cyc- S49 lymphoma cells

Biochem Pharmacol. 1988 Nov 15;37(22):4289-97. doi: 10.1016/0006-2952(88)90609-0.


beta-Adrenergic receptors on membranes prepared from L6 myoblasts, wild-type S49 lymphoma cells, and an adenylate cyclase-deficient variant (cyc-) of S49 lymphoma cells bind the agonist [3H]hydroxybenzylisoproterenol ([3H]HBI) with high affinity. In each case the agonist [3H]HBI is associated with a larger complex than is the antagonist [125I]iodopindolol, and the binding of [3H]HBI can be inhibited by GTP. These observations suggest that there is an agonist-dependent association of the receptor with a guanine nucleotide-binding protein. The goal of the present experiments was to investigate the possibility that an interaction of beta-adrenergic receptors with the inhibitory guanine nucleotide-binding protein of adenylate cyclase was responsible for these observations. Treatment of S49 cells with pertussis toxin decreased the extent of pertussis toxin-catalyzed [32P]ADP-ribosylation of a 41,000-dalton protein, measured in vitro, and decreased the inhibition of adenylate cyclase activity observed in the presence of somatostatin or analogues of GTP. Isoproterenol-stimulated adenylate cyclase activity was potentiated following treatment of wild-type S49 cells and L6 myoblasts with pertussis toxin. Although the ability of receptors on membranes prepared from L6 myoblasts to bind the agonist [3H]HBI was not affected by treatment of cells with pertussis toxin, treatment of cyc- S49 cells with pertussis toxin markedly decreased the ability of receptors to bind [3H]HBI. The observed inhibition of the binding of the agonist [3H]HBI to beta-adrenergic receptors on membranes prepared from cyc- S49 cells after treatment with pertussis toxin could be explained by an interaction between beta-adrenergic receptors and the inhibitory guanine nucleotide-binding protein. Such an interaction may represent a mechanism through which stimulation of the activity of adenylate cyclase by beta-adrenergic receptors can be regulated or through which beta-adrenergic receptors can affect the activity of cyclic AMP-independent cellular processes.

Publication types

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

MeSH terms

  • Adenosine Diphosphate Ribose / metabolism
  • Adenylate Cyclase Toxin
  • Adenylyl Cyclases / metabolism*
  • Animals
  • GTP-Binding Proteins / metabolism*
  • Isoproterenol / analogs & derivatives
  • Isoproterenol / metabolism
  • Lymphoma / metabolism*
  • Membranes / metabolism
  • Molecular Weight
  • NAD / metabolism
  • Pertussis Toxin
  • Pindolol / analogs & derivatives
  • Pindolol / metabolism
  • Receptors, Adrenergic, beta / metabolism*
  • Virulence Factors, Bordetella / pharmacology


  • Adenylate Cyclase Toxin
  • Receptors, Adrenergic, beta
  • Virulence Factors, Bordetella
  • NAD
  • Adenosine Diphosphate Ribose
  • hydroxybenzylisoproterenol
  • 3-iodopindolol
  • Pindolol
  • Pertussis Toxin
  • GTP-Binding Proteins
  • Adenylyl Cyclases
  • Isoproterenol