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Previously, (−)-trans-1-phenyl-3-N,N-dimethylamino-1,2,3,4-tetrahydronaphthalene ([−]-trans-H₂-PAT) was shown to activate stereospecifically histamine H₁ receptors coupled to modulation of tyrosine hydroxylase activity in guinea pig and rat forebrain in vitro and in vivo. Furthermore, the novel radioligand [³H](−)-trans-H₂-PAT was shown to label selectively H₁ receptors in guinea pig and rat brain with high affinity (K _D, ∼0.1 and 0.5 nM, respectively) and a B _max about 50 and 15%, respectively, of that observed for the H₁antagonist radioligand [³H]mepyramine. In the current study, [³H](−)-trans-H₂-PAT-labeled cloned guinea pig and human H₁ receptors in Chinese hamster ovary (CHO) cell membranes with high affinity (K _D, ∼0.08 and 0.23 nM, respectively) and a B _max about 15% of that observed for [³H]mepyramine. The binding of H₂-PAT to H₁ receptors in both CHO-H₁ cell lines was stereoselective with …