Sodium regulation of agonist and antagonist binding to beta-adrenoceptors in intact and Ns-deficient membranes.

Agonist binding to various hormone receptors mediating adenylate cyclase inhibition is decreased by sodium ions. We studied the influence of Na+ on agonist and antagonist binding to beta-adrenoceptors in membrane preparations of guinea pig lung, S49 lymphoma wild-type cells (WT) and their Ns-deficient cyc- variants by measuring binding of the antagonist, [125I]iodocyanopindolol [( 125I]CYP). At 37 degrees C, sodium decreased the receptor affinity for the agonist, isoproterenol, in all three membrane preparations. In lung and WT membranes, Na+ steepened the shallow agonist competition curves in a manner similar to and synergistic with guanine nucleotides. When binding was performed at 4 degrees C, sodium regulation but not guanine nucleotide regulation of agonist binding was preserved. At the low temperature, [125I]CYP affinity was reduced, and sodium increased [125I]CYP binding in both Ns-containing and Ns-deficient membranes by increasing the antagonist affinity without significant change in total receptor number. Compared to Na+, Li+ and K+ were much less potent and efficient in decreasing agonist and increasing antagonist binding. Na+ and Mg2+ had opposite effects on agonist binding in the Ns-containing lung and WT membranes but not in the Ns-deficient cyc- membranes. The data indicate that sodium not only regulates binding of inhibitory hormone receptors but also agonist and antagonist binding to the adenylate cyclase stimulatory beta-adrenoceptor. The finding that sodium regulation of beta-adrenoceptor binding is also observed in the Ns (alpha s)-deficient cyc- membranes, furthermore, indicates that the target of sodium is not the alpha-subunit of Ns but possibly a component common to both types of receptor systems regulating adenylate cyclase activity.