CRTH2-specific binding characteristics of [3H]ramatroban and its effects on PGD2-, 15-deoxy-Δ12, 14-PGJ2- and indomethacin-induced agonist responses

Hiromi Sugimoto, Michitaka Shichijo, Mitsuhiro Okano, Kevin B. Bacon

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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 Kd value (7.2 nM) to a TxA2 receptor (8.7 nM). We also demonstrated that ramatroban inhibited PGD 2-, 15-deoxy-Δ12, 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.

Original languageEnglish
Pages (from-to)30-37
Number of pages8
JournalEuropean Journal of Pharmacology
Volume524
Issue number1-3
DOIs
Publication statusPublished - Nov 7 2005

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Prostaglandins D
Indomethacin
Thromboxanes
varespladib methyl
Formyl Peptide Receptor
Th2 Cells
Eosinophils
Binding Sites
ramatroban
9-deoxy-delta-9-prostaglandin D2
Pharmacology
Calcium

Keywords

  • 15d-PGJ (15-deoxy-Δ -PGJ)
  • Competitive inhibitory effect
  • CRTH2 (Chemoattractant receptor-homologous molecule expressed on Th2 cells)
  • Indomethacin
  • Ramatroban

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

CRTH2-specific binding characteristics of [3H]ramatroban and its effects on PGD2-, 15-deoxy-Δ12, 14-PGJ2- and indomethacin-induced agonist responses. / Sugimoto, Hiromi; Shichijo, Michitaka; Okano, Mitsuhiro; Bacon, Kevin B.

In: European Journal of Pharmacology, Vol. 524, No. 1-3, 07.11.2005, p. 30-37.

Research output: Contribution to journalArticle

Sugimoto, Hiromi ; Shichijo, Michitaka ; Okano, Mitsuhiro ; Bacon, Kevin B. / CRTH2-specific binding characteristics of [3H]ramatroban and its effects on PGD2-, 15-deoxy-Δ12, 14-PGJ2- and indomethacin-induced agonist responses. In: European Journal of Pharmacology. 2005 ; Vol. 524, No. 1-3. pp. 30-37.
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