Labelling of non-H1-receptor binding sites by [3H]-mepyramine on the rat liver plasma membrane.
In the present study we characterized [3H]-mepyramine binding to rat liver plasma membranes. Binding of [3H]-mepyramine proved to be of high affinity (Kd = 7.7 +/- 0.4 nM) and saturable, resulting in a Bmax-value of 70.4 +/- 9.5 pmol/mg protein. However, displacement studies revealed that this binding site was different from other H1-receptor systems. The two stereoisomers of chlorpheniramine were rather ineffective in displacing [3H]-mepyramine and showed a stereospecificity in favour of the L-isomer. Also several H1-receptor agonists were not potent in displacing [3H]-mepyramine from rat liver plasma membranes. Moreover, the histamine metabolite imidazole-4-acetic acid was about as potent as the H1-agonists, whereas imidazole was even more potent. These data strongly suggest that [3H]-mepyramine labels a non-H1-receptor binding site on the rat liver plasma membrane.
Leurs
R
R
Department of Pharmacochemistry, Faculty of Chemistry, Vrije Universiteit, Amsterdam, The Netherlands.
Bast
A
A
Timmerman
H
H
D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D011506:Proteins / Q000378:metabolism; D011738:Pyrilamine / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011969:Receptors, Histamine H1 / Q000187:drug effects*; D013237:Stereoisomerism
D000631:Aminopyridines; D011506:Proteins; D011969:Receptors, Histamine H1; D011738:Pyrilamine