title: Distinctions in beta-adrenergic receptor interactions with the magnesium-guanine nucleotide coupling proteins in turkey erythrocyte and S49 lymphoma membranes.
abstract: Several homogeneous cell systems contain distinct subpopulations of beta-adrenergic receptors, distinguished by their relative sensitivity to N-ethylmaleimide (NEM) in the presence of agonist but not antagonist (G. Vauquelin and M.E. Maguire (1980) Mol. Pharmacol. 18, 363-369). The sensitivity to agonist/NEM inactivation requires receptor interaction with the magnesium-guanine nucleotide coupling proteins (G/F). We have investigated the effects of agonist/NEM treatment on Mg2+ and GTP modulation of receptor affinity in two such systems, turkey erythrocytes and murine S49 lymphoma cells. In each systems, the agonist/NEM-sensitive beta-receptor subpopulation exhibits both Mg2+ and GTP modulation of beta-receptor affinity for agonist. Further, Mg2+ and GTP are not competitive with regard to alteration of receptor affinity; that is, GTP can block the effect of Mg2+, but not vice versa. In contrast, the agonist/NEM-resistant beta-receptor subpopulation shows distinct differences in Mg2+ and GTP effects when the turkey and S49 systems are compared. The agonist/NEM-resistant population in S49 shows no effect of Mg2+ or GTP on beta-receptor affinity for agonist whereas the resistant beta-receptors of turkey erythrocytes still exhibit modulation by both GTP and Mg2+. Moreover, in this receptor population the actions of GTP and Mg2+ are apparently competitive, with increasing Mg2+ concentrations able to overcome the decrease in affinity induced by GTP. Thus, beta-receptor interaction with the metal/nucleotide coupling proteins may differ significantly in the two systems examined. An additional result of these experiments is the demonstration for S49 beta-receptors that free, unchelated GTP or GDP rather than MgGTP or MgGDP modulates receptor affinity for agonist.
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D004492:Edetic Acid / Q000494:pharmacology; D004910:Erythrocyte Membrane / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism*; D019204:GTP-Binding Proteins; D006150:Guanine Nucleotides / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008223:Lymphoma / Q000378:metabolism*; D008274:Magnesium / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D009374:Neoplasms, Experimental / Q000378:metabolism; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D014422:Turkeys
chemical_list: D001798:Blood Proteins; D006150:Guanine Nucleotides; D008565:Membrane Proteins; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D011956:Receptors, Cell Surface; D006160:Guanosine Triphosphate; D004492:Edetic Acid; D019204:GTP-Binding Proteins; D008274:Magnesium; D007545:Isoproterenol