Therapeutic efficacy of AM156, a novel prostanoid DP2 receptor antagonist, in murine models of allergic rhinitis and house dust mite-induced pulmonary inflammation
| Autor: | Yen Pham Truong, Peppi Prasit, Brian Andrew Stearns, Karin J. Stebbins, Alex R. Broadhead, Lucia Correa, Jilly F. Evans, Daniel S. Lorrain, Jill Melissa Scott, Hutchinson John H |
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| Rok vydání: | 2009 |
| Předmět: |
Benzylamines
Rhinitis Allergic Perennial medicine.drug_class Receptors Prostaglandin Thromboxane receptor chemistry.chemical_compound Mice Anti-Allergic Agents medicine Animals Eosinophil degranulation Receptors Immunologic Lung Asthma Pharmacology House dust mite Metaplasia Mice Inbred BALB C biology business.industry Pyroglyphidae Mucins Prostanoid Pneumonia respiratory system Eosinophil Immunoglobulin E medicine.disease biology.organism_classification Receptor antagonist Disease Models Animal medicine.anatomical_structure chemistry Immunology Cytokines lipids (amino acids peptides and proteins) Female Ramatroban business Bronchoalveolar Lavage Fluid medicine.drug |
| Zdroj: | European journal of pharmacology. 638(1-3) |
| ISSN: | 1879-0712 |
| Popis: | Prostaglandin D 2 (PGD 2 ) is derived from arachidonic acid and binds with high affinity to the G protein coupled receptors prostanoid DP 1 and DP 2 . Interaction with DP 2 results in cell chemotaxis, eosinophil degranulation, eosinophil shape change, adhesion molecule upregulation and Th2 cytokine production. In allergic rhinitis and allergic asthma PGD 2 is released from mast cells in response to allergen challenge and may trigger symptoms such as sneezing, rhinorrhea, pruritus, mucus hypersecretion and pulmonary inflammation. In Japan, ramatroban, a dual prostanoid DP 2 /prostanoid TP receptor antagonist, is marketed for allergic rhinitis while selective DP 2 antagonists are currently under investigation as therapeutics for asthma and allergic rhinitis. In the studies described herein, we investigated the efficacy of AM156, a novel selective prostanoid DP 2 receptor antagonist, in murine models of allergic rhinitis and asthma. AM156 inhibited sneezing and nasal rubs in a model of allergic rhinitis. AM156 inhibited pulmonary inflammation and mucus hypersecretion induced by chronic inhalation of house dust mite. These results suggest that selective prostanoid DP 2 receptor antagonists such as AM156 may provide beneficial effects for the clinical treatment of diseases such as allergic rhinitis and asthma. |
| Databáze: | OpenAIRE |
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