title: High affinity, saturable [3H]mepyramine binding sites on rat liver plasma membrane do not represent histamine H1-receptors. A warning.
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.
authors.affiliation: Department of Pharmacochemistry, Faculty of Chemistry, Vrije Universiteit, Amsterdam, the Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Leurs
authors.forename: A
authors.initials: A
authors.lastname: Bast
authors.forename: H
authors.initials: H
authors.lastname: Timmerman
mesh_terms: D000631:Aminopyridines / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D002462:Cell Membrane / Q000378:metabolism; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D011738:Pyrilamine / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011969:Receptors, Histamine H1 / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000631:Aminopyridines; D006634:Histamine H1 Antagonists; D011969:Receptors, Histamine H1; D011738:Pyrilamine