Cloning, Expression, and Pharmacological Characterization of a Novel Human Histamine Receptor
| العنوان: | Cloning, Expression, and Pharmacological Characterization of a Novel Human Histamine Receptor |
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| المؤلفون: | Vawter L, Derk J. Bergsma, Xiang Li, Shelagh Wilson, Robert S. Ames, Tierney La, Alston J, Boyce R, Hsiao-Ling Wu, Zhu Y, Henry M. Sarau, Fitzgerald Lr, George M. Dytko, Mannan Ij, J.P. Hieble, Nicole C. Herrity, Davenport Cm, Michalovich D, Tan Kb |
| المصدر: | Molecular Pharmacology. 59:434-441 |
| بيانات النشر: | American Society for Pharmacology & Experimental Therapeutics (ASPET), 2001. |
| سنة النشر: | 2001 |
| مصطلحات موضوعية: | Molecular Sequence Data, Gene Expression, Histamine H1 receptor, Biology, Pharmacology, Tritium, Mice, Radioligand Assay, chemistry.chemical_compound, Histamine receptor, Histamine H2 receptor, Genes, Reporter, Animals, Humans, Receptors, Histamine H3, Tissue Distribution, 5-HT5A receptor, Amino Acid Sequence, Histamine H4 receptor, Cloning, Molecular, Luciferases, Dose-Response Relationship, Drug, Sequence Homology, Amino Acid, Immepip, Cell biology, chemistry, Receptors, Histamine, Molecular Medicine, Calcium, Estrogen-related receptor gamma, Histamine H3 receptor, Histamine |
| الوصف: | 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)-alpha-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. |
| تدمد: | 1521-0111 0026-895X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1e8275e15c20f6649c1e6e629a7aa2a9 https://doi.org/10.1124/mol.59.3.434 |
| رقم الأكسشن: | edsair.doi.dedup.....1e8275e15c20f6649c1e6e629a7aa2a9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15210111 0026895X |
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