![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
INFLAMMATION AND IMMUNOPHARMACOLOGY
Bayer Yakuhin, Ltd., Research Center Kyoto, Respiratory Disease Research, Kyoto, Japan
We cloned, expressed, and characterized in vitro and in vivo the gene encoding the rat ortholog of chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2), a G protein-coupled receptor for prostaglandin D2 (PGD2). Quantitative reverse transcription-polymerase chain reaction analysis demonstrated highest CRTH2 expression in the lung, brain, ovary, and spleen. Pharmacologically, rat CRTH2 stably transfected in mouse preB lymphoma L1.2 cells behaved very similar compared with the mouse and human orthologs, showing a binding affinity for PGD2 of 11 nM, a functional calcium mobilization when exposed to agonist, and similar sensitivity to agonists and antagonists. In vivo, selective activation of CRTH2 by 13,14-dihydro-15-keto (DK)-PGD2 injection into rats led to a dose- and time-dependent increase of the number of leukocytes in the peripheral blood. Specifically, eosinophils, lymphocytes, and neutrophils were recruited with maximum effects seen 60 min after the injection of 300 µg of DK-PGD2 per rat. Pretreatment of the animals with the CRTH2/thromboxane A2 receptor antagonist, ramatroban, completely abrogated DK-PGD2-induced eosinophilia, suggesting that CRTH2 might have a physiological and/or pathophysiological role in controlling leukocyte migration.
Address correspondence to: Dr. F. Gantner, Bayer Yakuhin, Ltd., Research Center Kyoto, Respiratory Research, 6-5-1-3 Kunimidai, Kizu-cho, Sorakugun, 619-0216 Kyoto, Japan. E-mail: florian.gantner.fg{at}bayer.co.jp
This article has been cited by other articles:
|
|
 |
|
  R. Schroder, N. Merten, J. M. Mathiesen, L. Martini, A. Kruljac-Letunic, F. Krop, A. Blaukat, Y. Fang, E. Tran, T. Ulven, et al. The C-terminal Tail of CRTH2 Is a Key Molecular Determinant That Constrains G{alpha}i and Downstream Signaling Cascade Activation J. Biol. Chem., January 9, 2009; 284(2): 1324 - 1336. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Boehme, E. P. Chen, K. Franz-Bacon, R. Sasik, L. J. Sprague, T. W. Ly, G. Hardiman, and K. B. Bacon Antagonism of CRTH2 ameliorates chronic epicutaneous sensitization-induced inflammation by multiple mechanisms Int. Immunol., January 1, 2009; 21(1): 1 - 17. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Boehme, K. Franz-Bacon, E. P. Chen, R. Sasik, L. J. Sprague, T. W. Ly, G. Hardiman, and K. B. Bacon A small molecule CRTH2 antagonist inhibits FITC-induced allergic cutaneous inflammation Int. Immunol., January 1, 2009; 21(1): 81 - 93. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. W. Lukacs, A. A. Berlin, K. Franz-Bacon, R. Sasik, L. J. Sprague, T. W. Ly, G. Hardiman, S. A. Boehme, and K. B. Bacon CRTH2 antagonism significantly ameliorates airway hyperreactivity and downregulates inflammation-induced genes in a mouse model of airway inflammation Am J Physiol Lung Cell Mol Physiol, November 1, 2008; 295(5): L767 - L779. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Nomiya, M. Okano, T. Fujiwara, M. Maeda, Y. Kimura, K. Kino, M. Yokoyama, H. Hirai, K. Nagata, T. Hara, et al. CRTH2 Plays an Essential Role in the Pathophysiology of Cry j 1-Induced Pollinosis in Mice J. Immunol., April 15, 2008; 180(8): 5680 - 5688. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Sandig, J. E. Pease, and I. Sabroe Contrary prostaglandins: the opposing roles of PGD2 and its metabolites in leukocyte function J. Leukoc. Biol., February 1, 2007; 81(2): 372 - 382. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Aritake, Y. Kado, T. Inoue, M. Miyano, and Y. Urade Structural and Functional Characterization of HQL-79, an Orally Selective Inhibitor of Human Hematopoietic Prostaglandin D Synthase J. Biol. Chem., June 2, 2006; 281(22): 15277 - 15286. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. N. Hata, T. P. Lybrand, and R. M. Breyer Identification of Determinants of Ligand Binding Affinity and Selectivity in the Prostaglandin D2 Receptor CRTH2 J. Biol. Chem., September 16, 2005; 280(37): 32442 - 32451. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Chevalier, J. Stock, T. Fisher, M. Dupont, M. Fric, H. Fargeau, M. Leport, S. Soler, S. Fabien, M.-P. Pruniaux, et al. Cutting Edge: Chemoattractant Receptor-Homologous Molecule Expressed on TH2 Cells Plays a Restricting Role on IL-5 Production and Eosinophil Recruitment J. Immunol., August 15, 2005; 175(4): 2056 - 2060. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Mathiesen, T. Ulven, L. Martini, L. O. Gerlach, A. Heinemann, and E. Kostenis Identification of Indole Derivatives Exclusively Interfering with a G Protein-Independent Signaling Pathway of the Prostaglandin D2 Receptor CRTH2 Mol. Pharmacol., August 1, 2005; 68(2): 393 - 402. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Almishri, C. Cossette, J. Rokach, J. G. Martin, Q. Hamid, and W. S. Powell Effects of Prostaglandin D2, 15-Deoxy-{Delta}12,14-prostaglandin J2, and Selective DP1 and DP2 Receptor Agonists on Pulmonary Infiltration of Eosinophils in Brown Norway Rats J. Pharmacol. Exp. Ther., April 1, 2005; 313(1): 64 - 69. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Shiraishi, K. Asano, T. Nakajima, T. Oguma, Y. Suzuki, T. Shiomi, K. Sayama, K. Niimi, M. Wakaki, J. Kagyo, et al. Prostaglandin D2-Induced Eosinophilic Airway Inflammation Is Mediated by CRTH2 Receptor J. Pharmacol. Exp. Ther., March 1, 2005; 312(3): 954 - 960. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. N. Hata, T. P. Lybrand, L. J. Marnett, and R. M. Breyer Structural Determinants of Arylacetic Acid Nonsteroidal Anti-Inflammatory Drugs Necessary for Binding and Activation of the Prostaglandin D2 Receptor CRTH2 Mol. Pharmacol., March 1, 2005; 67(3): 640 - 647. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Takeshita, T. Yamasaki, K. Nagao, H. Sugimoto, M. Shichijo, F. Gantner, and K. B. Bacon CRTH2 is a prominent effector in contact hypersensitivity-induced neutrophil inflammation Int. Immunol., July 1, 2004; 16(7): 947 - 959. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
