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

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Leurs R, Bast A, Timmerman H

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

Biochem Pharmacol. 1989 Jul 1;38(13):2175-80.

PubMed ID

2567596 [ View in PubMed

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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 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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Pheniramine	Histamine H1 receptor	Protein	Humans	Yes	Inverse agonist	Details