Pharmacological characterization of guinea pig chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2)

• Published in: Prostaglandins & other lipid mediators Vol. 76; no. 1; pp. 133 - 147
• Main Authors: Liu, Fang, Gonzalo, Jose Angel, Manning, Stephen, O’Connell, Laura E., Fedyk, Eric R., Burke, Kristine E., Elder, Amy M., Pulido, Jacqueline C., Cao, Wei, Tayber, Olga, Qiu, Yubin, Ghosh, Shomir, Ocain, Timothy D., Hodge, Martin R., Suzuki-Yagawa, Yuriko
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2005
• Subjects: Allergic inflammation; Animals; Base Sequence; Calcium - metabolism; Cell Line; Chemotaxis, Leukocyte; Cloning, Molecular; DNA Primers; DNA, Complementary; Eosinophils - cytology; Gene cloning and expression; Guinea pig CRTH2; Guinea Pigs; Humans; Lung - metabolism; Lymph Nodes - metabolism; Male; Pharmacology; Prostaglandin D 2 (PGD 2); Receptors, Immunologic - genetics; Receptors, Immunologic - metabolism; Receptors, Prostaglandin - genetics; Receptors, Prostaglandin - metabolism; Spleen - metabolism; Thymus Gland - metabolism; Δ 12-PGJ 2; Guinea pig CRTH2; 15d-PGJ 2; Allergic inflammation; BW245C; SPA; DMSO; Pharmacology; Prostaglandin D 2 (PGD 2); DP; DK-PGD 2; RT-PCR; CRTH2; Gene cloning and expression; PCR; Δ 12-PGJ 2
• ISSN: 1098-8823
• DOI: 10.1016/j.prostaglandins.2005.03.001

Chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2), a G protein-coupled receptor activated by prostaglandin D 2 (PGD 2), has been identified as a receptor expressed on cell types critical to the pathogenesis of asthma. The cDNA encoding guinea pig CRTH2 was cloned and mRNA expression examined in selected tissues. Transcript profiling of guinea pig CRTH2 indicated relatively high levels of expression in bone marrow, intermediate levels in brain and relatively low levels in lung, spleen, thymus, lymph node, etc. Characterization of the molecular pharmacology of guinea pig CRTH2 revealed that guinea pig CRTH2 exhibited a greater affinity for Δ 12-PGJ 2, a stable PGD 2 metabolite relative to human CRTH2. The CRTH2 selective agonists 13,14-dihydro-15-keto PGD 2 and Δ 12-PGJ 2 induced the recruitment of eosinophils following intradermal administration of these ligands in guinea pigs. Chemotaxis of guinea pig eosinophils was elicited by either PGD 2 or Δ 12-PGJ 2, and was abolished by a CRTH2-specific antagonist. These results indicate that PGD 2 and the stable metabolite, Δ 12-PGJ 2, play important roles in CRTH2 activation in the guinea pig.