CRTH2-specific binding characteristics of [³H]ramatroban and its effects on PGD₂-, 15-deoxy-Δ^{12, 14}-PGJ₂- and indomethacin-induced agonist responses

We previously showed that ramatroban (Baynas™), a thromboxane A ₂ (TxA₂) antagonist, had inhibited prostaglandin D ₂ (PGD₂)-stimulated human eosinophil migration mediated through activation of chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2). However, detailed pharmacological characterization of its inhibitory activity has not been described. In the present study, we showed that [³H]ramatroban bound to a single receptor site on CRTH2 transfectants with a similar K_d value (7.2 nM) to a TxA₂ receptor (8.7 nM). We also demonstrated that ramatroban inhibited PGD ₂-, 15-deoxy-Δ^{12, 14}-PGJ₂ (15d-PGJ ₂)- and indomethacin-induced calcium responses on CRTH2 transfectants in a competitive manner with similar pA₂ values (8.5, 8.5, and 8.6, respectively). This is the first report showing the evidence for direct binding of ramatroban to CRTH2, revealing its competitive inhibitory effects and another interesting finding that PGD₂, indomethacin and 15d-PGJ₂ share the same binding site with ramatroban on CRTH2.