INHIBITION BY CATIONS OF ANTAGONIST BINDING TO HISTAMINE H1-RECEPTORS - DIFFERENTIAL EFFECT OF SODIUM-IONS ON THE BINDING OF 2 RADIOLIGANDS

1 Measurements have been made of the inhibition by mono- and divalent cations of the binding of [H-3]-(+)-N-methyl-4-methyldiphenhydramine ([H-3]-QMDP) to histamine H-1 receptors in homogenates of guinea-pig cerebellum. 2 The binding of [H-3]-QMDP was inhibited by monovalent cations with an order of potency Li+ = Na+ > K+ > Cs+ = Rb+. The IC50 for Li+ was 39 mM, but that for K+ was 132 mM. Hill coefficients for inhibition curves for Li+ and Na+ were < 1. 3 Divalent cations also inhibited the binding of [H-3]-QMDP. The most potent cations examined were Hg2+, Cd2+ and Zn2+, with IC50 values of 5, 17 and 41-mu-M, respectively. Ca2+ and Mg2+ were relatively weak inhibitors (IC50 12 and 34 mM, respectively). The potency of Ni2+, Co2+ and Mn2+ was intermediate between these groups. Hill coefficients for inhibition curves for Hg2+, Cd2+ and Zn2+ were > 1, but Hill coefficients for the other cations were < 1. 4 Both mono- and divalent cations also inhibited the binding of [H-3]-mepyramine. The divalent cations were approximately equipotent in inhibiting the binding of [H-3]-QMDP and [H-3]-mepyramine. The same was true for Li+. However, Na+ was markedly more effective against [H-3]-QMDP binding than against the binding of [H-3]-mepyramine. 5 The effect of 40 mM Li+ on the parameters of binding of [H-3]-mepyramine was to increase the best-fit value of the concentration giving half-maximal binding EC50, by approximately 2 fold without having any significant effect on the maximum amount of binding. Cd2+ (15-mu-M) caused both an increase in EC50 and a decrease in B(max) (32 +/- 4% inhibition). Na+, 100 mM, had no significant effect on either EC50 or B(max) for [H-3]-mepyramine binding.