Effects of cations on high-affinity binding of 3H-ADTN to dopaminergic sites in calf caudate tissue

Effects of cations on binding of 0.1-10 nM 3H-ADTN to calf caudate membranes included decreased apparent Bmax by [Na+] greater than or equal to 100 mM, little effect on Kd or on affinity of other dopamine (DA) agonists (DA and apomorphine), decreased slopes of inhibition curves produced by agonists, but increased affinity of the antagonists (+)butaclamol; in contrast, low (10-20 mM) [Na+] did not decrease Bmax, increased ligand and agonist affinity and specific binding, and gave steep monophasic inhibition curves for DA agonists. K+, Li+, and Rb+ had little effect at a wide range of concentrations. Mg++ and Ca++, in physiologic concentrations, moderately increased binding of 3H-ADTN, as did microM Mn++ or Co++; the latter ions inhibited binding at greater than or equal to 10 mM, as did Cu++ (IC50 = 10 microM). The results extend impressions that physiologic [Na+] favors binding of DA antagonists and diminishes binding of agonists, but optimal agonist binding occurred at low [Na+] (10-20 mM), while divalent cations had complex actions.