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 (K _d =7.7±0.4 nM) and saturable, resulting in a B_max-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 stercospecificity in favour of thel-isomer. Also several H₁-receptor agonists were not potent in displacing ³H]-mepyramine from rat liver plasma membranes. Morcover, 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.