Binding of 4(5)-[2-(4-Azido-2-nitroanilino)ethyl]imidazole to Histamine Receptors in Guinea Pig Cerebral Cortical Membranes 1

Abstract

The interaction of 4(5)-[2-(4-azido-2-nitroanilino)ethyl]imidazole (AAH), a photolabile histamine receptor antagonist, with the binding of histamine, mepyramine, and tiotidine to guinea pig cerebral cortical membranes was examined to evaluate the specificity of AAH for histamine H₁ and H₂ receptors. Saturable, specific binding of [³H]histamine, [³H]mepyramine, and [³H]tiotidine to the membranes was observed. Competition assays were used to assess the relative affinity of AAH for H₁- and H₂-receptors. The rank order of IC₅₀ values obtained was (most to least potent) (i) for competing with [³H]histamine binding: histamine > AAH ≫ mepyramine ≃ tiotidine; (ii) for competing with [³H]mepyramine binding: mepyramine ≫ AAH ≃ histamine > tiotidine; and (iii) for competing with [³H]tiotidine binding: tiotidine ≫ mepyramine > histamine ≃ AAH. The affinity of AAH for H₁ receptors was ca. 14-fold greater than for H₂ receptors. These findings support previous evidence obtained in isolated smooth muscle preparations that AAH shows H₁-receptor selectivity as an antagonist.