Selective interaction of beta 2- and alpha 2-adrenergic receptors with stimulatory and inhibitory guanine nucleotide-binding proteins.
In Chinese hamster ovary cells expressing recombinant beta 2-adrenergic receptors, isoproterenol enhanced cholera toxin-catalyzed ADP-ribosylation of the large form of G5 alpha. The effect was stereoselectively blocked by the enantiomers of propranolol, indicating receptor mediation. The ADP-ribosylated form of Gs alpha-subunit was resolved into a triplet in gradient gels. beta 2-Adrenergic receptors increased both the labelling and the apparent mass of the slower migrating forms of large Gs alpha, as determined by autoradiography and immunoblotting, suggesting that Gs alpha, can incorporate more than one ADP-ribose per molecule. In cells coexpressing similar amounts of beta 2-adrenergic, alpha 2-adrenergic, and m1 muscarinic receptors, beta 2 receptors stimulated the ADP-ribosylation of only large Gs and alpha 2 receptors that of only Gi; muscarinic receptors had no apparent effect. Thus, in native membranes there appears to be a selectivity for the interaction between adrenergic receptor subtypes and Gs alpha or Gi alpha subunits.
Ogino
Y
Y
Laboratory of Theoretical and Physical Biology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.
Fraser
C M
CM
Costa
T
T
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D015153:Blotting, Western; D016466:CHO Cells; D002772:Cholera Toxin / Q000494:pharmacology; D006224:Cricetinae; D004591:Electrophoresis, Polyacrylamide Gel; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism
D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D011994:Recombinant Proteins; D000246:Adenosine Diphosphate Ribose; D002772:Cholera Toxin; D019204:GTP-Binding Proteins; D007545:Isoproterenol