Chemoattractant receptor-homologous molecule on Th2 cells (CRTH2) receptors belong to a distinct family from the family of other prostanoid receptors. CRTH2 receptors are reported to be mainly coupled to Gi protein, but also to Gq protein. Prostaglandin (PG) D₂ is considered as the major ligand of CRTH2 receptors, however, the metabolites of PGD₂ are also known to activate CRTH2 receptors although the detailed mechanisms haven't been elucidated.
In this study, we aimed to elucidate the functional differences of CRTH2 receptors-mediated signaling activate by PGJ₂, a major metabolite of PGD₂.
Using HEK293 cells stably expressing CRTH2 receptors, the effects of PGJ₂ on cAMP formations as well as intracellular Ca²⁺ concentrations were examined.
As the results, PGJ₂ showed little inhibition of cAMP formation when compared to PGD₂, possibly because of lower affinity to the receptors. However, PGJ₂ could induce similar levels of the intracellular Ca²⁺ concentration as that was induced by PGD₂. Since PGD₂ has been reported to exacerbate allergic inflammations such as asthma by acting on CRTH2 receptors, its metabolite PGJ₂ could augment allergic reaction, by sustaining Ca²⁺-mediated construction of brouchial tubes as a biased ligand of the receptors.