HETEROGENEITY OF [H-3] MEPYRAMINE BINDING-SITES IN GUINEA-PIG CEREBELLUM AND LUNG

The nature of histamine receptors in peripheral tissues is still controversial. However, evidence of heterogeneous classes of binding sites for [H-3]-mepyramine are reported in the literature. The aim of our study was, therefore, to investigate the nature of this heterogeneity by comparing [H-3]-mepyramine binding in a central tissue (cerebellum) and in a peripheral tissue (lung) obtained from guinea pigs and to assess its dependence upon the temperature of incubation. The results revealed that the [H-3]-mepyramine interaction in both tissues is temperature-dependent. At 25-degrees-C, the interaction between [H-3]-mepyramine and the receptors was biphasic in the lung while only a single class of binding site was found in the cerebellum. At 0-degrees-C, [H-3]-mepyramine interacted with three binding sites in the lung and two in the cerebellum. The behaviour of the reference compounds (clemastine, promethazine and histamine) also supported this temperature-dependence. Moreover, two new compounds (DF 11062 and DF 11113), synthesized in our laboratories and endowed with antihistamine activity, can differentiate between the low affinity site seen at 25-degrees-C in the lung and that seen in the cerebellum at 0-degrees-C.