An orally bioavailable small molecule antagonist of CRTH2, ramatroban (BAY u3405), inhibits prostaglandin D2-induced eosinophil migration in vitro
| Autor: | Florian Gantner, Hiromi Sugimoto, Makoto Shimazaki, Michitaka Shichijo, Kevin Bacon, Takashi Iino, Yoshihisa Manabe, Akihiko Watanabe |
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| Rok vydání: | 2003 |
| Předmět: |
Receptors
Prostaglandin Carbazoles Prostaglandin Administration Oral Biological Availability Pharmacology In Vitro Techniques Transfection chemistry.chemical_compound Eosinophil migration Cell Movement Eosinophil activation medicine Humans Drug Interactions Receptors Immunologic Prostaglandin D2 receptor Sulfonamides Prostaglandin D2 respiratory system Eosinophil Eosinophils medicine.anatomical_structure chemistry Mechanism of action Molecular Medicine Calcium Ramatroban medicine.symptom Platelet Aggregation Inhibitors medicine.drug |
| Zdroj: | The Journal of pharmacology and experimental therapeutics. 305(1) |
| ISSN: | 0022-3565 |
| Popis: | Ramatroban (Baynas, BAY u3405), a thromboxane A(2) (TxA(2)) antagonist marketed for allergic rhinitis, has been shown to partially attenuate prostaglandin (PG)D(2)-induced bronchial hyperresponsiveness in humans, as well as reduce antigen-induced early- and late-phase inflammatory responses in mice, guinea pigs, and rats. PGD(2) is known to induce eosinophilia following intranasal administration, and to induce eosinophil activation in vitro. In addition to the TxA(2) receptor, PGD(2) is known as a ligand for the PGD(2) receptor, and the newly identified G-protein-coupled chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2). To fully characterize PGD(2)-mediated inflammatory responses relevant to eosinophil activation, further analysis of the mechanism of action of ramatroban has now been performed. PGD(2)-stimulated human eosinophil migration was shown to be mediated exclusively through activation of CRTH2, and surprisingly, these effects were completely inhibited by ramatroban. This is also the first report detailing an orally bioavailable small molecule CRTH2 antagonist. Our findings suggest that clinical efficacy of ramatroban may be in part mediated through its action on this Th2-, eosinophil-, and basophil-specific chemoattractant receptor. |
| Databáze: | OpenAIRE |
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