Inhibition of antigen-induced airway inflammation and hyperresponsiveness in guinea pigs by a selective antagonist of “chemoattractant receptor homologous molecule expressed on Th2 cells” (CRTH2)

• Published in: European journal of pharmaceutical sciences 2013-06, Vol.49 (3), p.434-440
• Main Authors: Tasaki, Mamoru, Kobayashi, Miki, Tenda, Yoshiyuki, Tsujimoto, Susumu, Nakazato, Shoko, Numazaki, Mako, Hirano, Yasuno, Matsuda, Hiroshi, Terasaka, Tadashi, Miyao, Yasuhiro, Shimizu, Yasuaki, Hirayama, Yoshitaka
• Format: Article
• Language: English
• Subjects: Airway hyper responsiveness; Animals; Anti-Asthmatic Agents - pharmacology; Anti-Asthmatic Agents - therapeutic use; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Antigens; ASP5642; Benzhydryl Compounds - pharmacology; Benzhydryl Compounds - therapeutic use; Bronchial Hyperreactivity - drug therapy; Bronchial Hyperreactivity - immunology; Bronchoalveolar Lavage Fluid - cytology; Carbazoles - therapeutic use; Cell Count; Chemoattractant receptor homologous molecule expressed on T helper type 2 cells; Eosinophilia - chemically induced; Eosinophilia - drug therapy; Guinea pig; Guinea Pigs; HEK293 Cells; Humans; K562 Cells; Male; Ovalbumin; Pneumonia - drug therapy; Pneumonia - immunology; Prostaglandin D2; Pyridazines - pharmacology; Pyridazines - therapeutic use; Receptors, Immunologic - antagonists & inhibitors; Receptors, Prostaglandin - antagonists & inhibitors; Sulfonamides - therapeutic use
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2013.04.017

Chemoattractant receptor homologous molecule expressed on T helper type 2 cells (CRTH2) is a PGD2 receptor found on eosinophils, basophils, and Th2 type T cells which exhibits chemotaxis and functions in activation cascades. However, while a number of CRTH2 antagonists, including ramatroban, are known to exert activity in certain animal models, activity in a guinea pig model of EA-induced airway hyperresponsiveness has not been demonstrated. The newly developed CRTH2 antagonist ASP5642 has shown antagonistic activity against human and guinea pig CRTH2 in previous studies and has also been found effective in treating guinea pig models of airway inflammation and airway hyperresponsiveness. While previous studies have used animals such as rats and mice to evaluate CRTH2 antagonist effects, ours is the first attempt to evaluate CRTH2 function in a guinea pig asthma model, which may prove useful in evaluating the compound’s effects in humans, given the comparable airway function between the two species taken together, these data from the present study strongly suggest the utility of ASP5642 in investigating the role of CRTH2 in inflammatory responses and as a drug treatment for human asthma.