TY - JOUR T1 - Cloning, Expression, and Pharmacological Characterization of a Novel Human Histamine Receptor JF - Molecular Pharmacology JO - Mol Pharmacol SP - 434 LP - 441 DO - 10.1124/mol.59.3.434 VL - 59 IS - 3 AU - Yuan Zhu AU - David Michalovich AU - Hsiao-Ling Wu AU - K. B. Tan AU - George M. Dytko AU - Ishrat J. Mannan AU - Rogely Boyce AU - James Alston AU - Lauren A Tierney AU - Xiaotong Li AU - Nicole C. Herrity AU - Lisa Vawter AU - Henry M. Sarau AU - Robert S. Ames AU - Colleen M. Davenport AU - J. Paul Hieble AU - Shelagh Wilson AU - Derk J. Bergsma AU - Laura R. Fitzgerald Y1 - 2001/03/01 UR - http://molpharm.aspetjournals.org/content/59/3/434.abstract N2 - Using a genomics-based reverse pharmacological approach for screening orphan G-protein coupled receptors, we have identified and cloned a novel high-affinity histamine receptor. This receptor, termed AXOR35, is most closely related to the H3 histamine receptor, sharing 37% protein sequence identity. A multiple responsive element/cyclic AMP-responsive element-luciferase reporter assay was used to identify histamine as a ligand for AXOR35. When transfected into human embryonic kidney 293 cells, the AXOR35 receptor showed a strong, dose-dependent calcium mobilization response to histamine and H3 receptor agonists including imetit and immepip. Radioligand binding confirmed that the AXOR35 receptor was a high-affinity histamine receptor. The pharmacology of the AXOR35 receptor was found to closely resemble that of the H3 receptor; the major difference was that (R)-α-methylhistamine was a low potency agonist of the AXOR35 receptor. Thioperamide is an antagonist at AXOR 35. Expression of AXOR35 mRNA in human tissues is highest in peripheral blood mononuclear cells and in tissues likely to contain high concentrations of blood cells, such as bone marrow and lung. In situ hybridization analysis of a wide survey of mouse tissues showed that mouse AXOR35 mRNA is selectively expressed in hippocampus. The identification and localization of this new histamine receptor will expand our understanding of the physiological and pathological roles of histamine and may provide additional opportunities for pharmacological modification of these actions. ER -