The Gs protein coupled D type prostanoid (DP) receptors have been known to exhibit anti-inflammatory effects.
The DP receptors are well recognized as cognate receptors for prostaglandin (PG)D₂, which is known to be involved in inflammatory responses and allergies.
There are five endogeneous metabolites of PGD₂; PGJ₂, Δ¹²-PGJ₂, 13,14-dihydro-15-keto-PGD₂, 15-deoxy-Δ^12,14-PGD₂, and 15-deoxy-Δ^12,14-PGJ₂.
Previously, we showed that 15-keto-PGE₂, a metabolite of PGE₂, acts on EP2 and EP4 receptors as biased agonist, and plays a role on switching cellular signalings mediated from EP4 receptors to EP2 receptors.
Therefore, we here examined if PGD₂ and these five metabolites act on DP receptors as biased agonists, and found out they showed different profiles in terms of DP receptor activities.
Thus, PGD₂ and PGJ₂ acted as full agonists with similar potencies, whereas, Δ¹²-PGJ₂ acted as a partial agonist to the cAMP system and T cell factor/β-catenin transcriptional activity.
These results suggest that the metabolites of PGD₂ are not simply inactivated metabolites, but may have some physiological significance in the inflammatory response mediated by DP receptors.