Inhibition by cations of antagonist binding to histamine H1‐receptors: differential effect of sodium ions on the binding of two radioligands

Abstract

Measurements have been made of the inhibition by mono‐ and divalent cations of the binding of [3H]‐(+)‐N‐methyl‐4‐methyldiphenhydramine ([3H]‐QMDP) to histamine H1‐receptors in homogenates of guinea‐pig cerebellum. The binding of [3H]‐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. Divalent cations also inhibited the binding of [3H]‐QMDP. The most potent cations examined were Hg2+, Cd2+ and Zn2+, with IC50 values of 5, 17 and 41 μm, 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. Both mono‐ and divalent cations also inhibited the binding of [3H]‐mepyramine. The divalent cations were approximately equipotent in inhibiting the binding of [3H]‐QMDP and [3H]‐mepyramine. The same was true for Li+. However, Na+ was markedly more effective against [3H]‐QMDP binding than against the binding of [3H]‐mepyramine. The effect of 40 mm Li+ on the parameters of binding of [3H]‐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 μm) caused both an increase in EC50 and a decrease in Bmax (32 ± 4% inhibition). Na+, 100 mm, had no significant effect on either EC50 or Bmax for [3H]‐mepyramine binding. 1991 British Pharmacological Society