Heterogeneity of [3H]-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 [3H]-mepyramine are reported in the literature. The aim of our study was, therefore, to investigate the nature of this heterogeneity by comparing [3H]-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 [3H]-mepyramine interaction in both tissues is temperature-dependent. At 25 degrees C, the interaction between [3H]-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, [3H]-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.
Dini
S
S
Research and Development Laboratories, Dompé Farmaceutici S.p.A., Milano, Italy.
Caselli
G F
GF
Ferrari
M P
MP
Giani
R
R
Clavenna
G
G
D000818:Animals; D001562:Benzimidazoles / Q000378:metabolism; D001667:Binding, Competitive; D002531:Cerebellum / Q000378:metabolism*; D006168:Guinea Pigs; D006633:Histamine Antagonists / Q000378:metabolism*; D007700:Kinetics; D008168:Lung / Q000378:metabolism*; D008297:Male; D011725:Pyridines / Q000378:metabolism; D011738:Pyrilamine / Q000378:metabolism*; D011869:Radioligand Assay; D011968:Receptors, Histamine / Q000378:metabolism*; D013696:Temperature; D014316:Tritium
D001562:Benzimidazoles; D006633:Histamine Antagonists; D011725:Pyridines; D011968:Receptors, Histamine; D014316:Tritium; C070878:DF 11062; C070877:DF 11113; D011738:Pyrilamine