Elsevier

Biochemical Pharmacology

Volume 38, Issue 13, 1 July 1989, Pages 2175-2180
Biochemical Pharmacology

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

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Abstract

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 mol/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 μM) was even more potent than its H1-selective 2-methylderivative (Ki = 772 μM). 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.

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