G-Protein-Coupled Receptor 35 Is a Target of the Asthma Drugs Cromolyn Disodium and Nedocromil Sodium
| Autor: | Jeff D. Reagan, Shamin Summer, Yuhua Yang, Jenny Ying-Lin Lu, Christiaan J. M. Saris, John Whoriskey, Xiaosu Wu |
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| Rok vydání: | 2010 |
| Předmět: |
Agonist
medicine.medical_specialty Purinones medicine.drug_class In Vitro Techniques Pharmacology Immunoglobulin E Receptors G-Protein-Coupled Mice chemistry.chemical_compound Drug Delivery Systems Nedocromil Cricetinae Internal medicine Cromolyn Sodium Calcium flux medicine Animals Humans Anti-Asthmatic Agents Mast Cells RNA Messenger Nedocromil Sodium Receptor biology Chemistry General Medicine Phosphodiesterase 5 Inhibitors respiratory system Mast cell Basophils Rats respiratory tract diseases Eosinophils Endocrinology medicine.anatomical_structure cGMP-specific phosphodiesterase type 5 biology.protein Zaprinast |
| Zdroj: | Pharmacology. 86:1-5 |
| ISSN: | 1423-0313 0031-7012 |
| DOI: | 10.1159/000314164 |
| Popis: | We report that the asthma drugs cromolyn disodium and nedocromil sodium are potent G-protein-coupled receptor 35 (GPR35) agonists. We utilized calcium flux and inositol phosphate accumulation assays to examine the pharmacology of these asthma drugs on the human, mouse and rat GPR35. The compounds were more potent on the human GPR35 than on mouse and rat receptors. In contrast, zaprinast, a known GPR35 agonist, was more potent on mouse and rat GPR35 than the human ortholog. We show by quantitative PCR that GPR35 is expressed in human mast cells, human basophils and human eosinophils. We also demonstrate that GPR35 mRNA is upregulated upon challenge with IgE antibodies. We show that, unlike zaprinast, a potent phosphodiesterase 5 (PDE5) inhibitor, cromolyn disodium and nedocromil sodium lack inhibitory activity towards PDE5. These findings suggest that GPR35 may play an important role in mast cell biology and be a potential target for the treatment of asthma. |
| Databáze: | OpenAIRE |
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