Characteristics of recombinantly expressed rat and human histamine H3 receptors

Human and rat histamine H-3 receptors were recombinantly expressed and characterized using receptor binding and a functional cAMP assay. Seven of nine agonists had similar affinities and potencies at the rat and human histamine H-3 receptor. S-alpha-methylhistamine had a significantly higher affinity and potency at the human than rat receptor, and for 4-[(1R*,2R*)-2-(5,5-dimethyl-1-hexynyl)cyclopropyl]-1H-imidazole (Perceptin((R))) the preference was the reverse. Only two of six antagonists had similar affinities and potencies at the human and the rat histamine H-3 receptor. Ciproxifan, thioperamide and (1R*,2R*)-trans-2-imidazol-4 ylcyclopropyl) (cyclohexylmethoxy) carboxamide (GT2394) had significantly higher affinities and potencies at the rat than at the human histamine H-3 receptor, while for N-(4-chlorobenzyl)-N-(7-pyrrolodin-1-ylheptyl)guanidine (JB98064) the preference was the reverse. All antagonists also showed potent inverse agonism properties. Iodoproxyfan, Perceptin((R)), proxyfan and GR175737, compounds previously described as histamine H-3 receptor antagonists, acted as full or partial agonists at both the rat and the human histamine H-3 receptor. (C) 2002 Elsevier Science B.V. All rights reserved.