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Inhibition by cations of antagonist binding to histamine H 1 ‐receptors: differential effect of sodium ions on the binding of two radioligands

1991; Wiley; Volume: 103; Issue: 3 Linguagem: Inglês

10.1111/j.1476-5381.1991.tb09857.x

1476-5381

J. Mark Treherne, J.S. Stern, W.J. Flack, J.M. Young,

Chemical Synthesis and Analysis

1 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. 2 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. 3 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. 4 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. 5 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.