High affinity, saturable [3H]mepyramine binding sites on rat liver plasma membrane do not represent histamine H1-receptors. A warning.

R Leurs, A Bast, H Timmerman

Department of Pharmacochemistry, Faculty of Chemistry, Vrije Universiteit, Amsterdam, the Netherlands.

Biochemical pharmacology 1989 Jul 1

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Rat liver plasma membrane contains a saturable, high affinity binding site for the labelled histamine H1-antagonist [3H]mepyramine. Nonlinear regression analysis of the performed saturation experiments revealed an equilibrium dissociation constant (Kd) of 7.7 +/- 0.4 nM and a maximal binding capacity (Bmax) of 70.4 +/- 9.5 pmol/mg protein. Specific binding could be inhibited completely by several histaminergic ligands. However, the affinities of the tested H1-antagonists other than mepyramine for this binding site were quite low and the known stereospecificity displayed by the histamine H1-receptor for the enantiomers of chlorpheniramine and pheniramine was not found. Moreover, the H2-selective agonist 4-methylhistamine (Ki = 412 microM) was even more potent than its H1-selective 2-methylderivative (Ki = 772 microM). Since several ethylenediamines were also very potent in displacing [3H]mepyramine we suggest the presence of an ethylenediamine recognition site on rat liver plasma membrane which is unrelated to the histamine H1-receptor. It is stressed that a proper pharmacological characterization of a reported binding site is needed, since we show in this study that [3H]mepyramine, which is frequently used in studies concerning the H1-receptor, labels non-H1-receptor binding sites in rat liver plasma membrane.

Citation

R Leurs, A Bast, H Timmerman. High affinity, saturable [3H]mepyramine binding sites on rat liver plasma membrane do not represent histamine H1-receptors. A warning. Biochemical pharmacology. 1989 Jul 1;38(13):2175-80