PT  - JOURNAL ARTICLE
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
TI  - Cloning, Expression, and Pharmacological Characterization of a Novel Human Histamine Receptor
AID  - 10.1124/mol.59.3.434
DP  - 2001 Mar 01
TA  - Molecular Pharmacology
PG  - 434--441
VI  - 59
IP  - 3
4099  - http://molpharm.aspetjournals.org/content/59/3/434.short
4100  - http://molpharm.aspetjournals.org/content/59/3/434.full
SO  - Mol Pharmacol2001 Mar 01; 59
AB  - 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.