Many of the effects of prostaglandin D
2 (PGD
2) are transduced
via a traditional 7-
transmembrane GPCR, the DP
1 receptor.
1 However, in certain leukocytes and other immune cells, a second PGD
2 receptor referred to as the CRTH2 or DP
2 receptor has been cloned and characterized.
2,3 15(R)-
15-
methyl PGD
2 is a surprisingly potent agonist at the DP
2 receptor, being about 5 times more potent than PGD
2 itself.
4 15(R)-
PGD
2 has the potential to be produced endogenously as a natural ligand for DP
2, unlike the synthetic 15-
methyl analogs. In preliminary reports, 15(R)-
PGD
2 has also been reported to be a potent and selective DP
2 receptor agonist.
5,6
1. Boie, Y., Sawyer, N., Slipetz, D.M., et al. Molecular cloning and characterization of the human prostanoid DP receptor J. Biol. Chem. 270(32),18910-18916(1995).
2. Abe, H., Takeshita, T., Nagata, K., et al. Molecular cloning, chromosome mapping and characterization of the mouse CRTH2 gene, a putative member of the leukocyte chemoattractant receptor family Gene 227,71-77(1999).
3. Hirai, H., Tanaka, K., Yoshie, O., et al. Prostaglandin D2 selectivity induces chemotaxis in T helper type 2 cells, eosinophils, and basophils via seven-transmembrane receptor CRTH2 J. Exp. Med. 193(2),255-261(2001).
4. Monneret, G., Cossette, C., Gravel, S., et al. 15R-methyl-prostaglandin D2 is a potent and selective CRTH2/DP2 receptor agonist in human eosinophils J. Pharmacol. Exp. Ther. 304(1),349-355(2003).
5. Kim, S., Bellone, S., Maxey, K.M., et al. Synthesis of 15R-PGD2: A potential DP2 receptor agonist Bioorg. Med. Chem. Lett. 15(7),1873-1876(2005).
6. Cossette, C., Walsh, S.E., Kim, S., et al. Agonist and antagonist effects of 15R-prostaglandin (PF) D2 and 11-methylene-PGD2 on human eosinophils and basophils J. Pharmacol. Exp. Ther. 320(1),173-179(2007).
