Identification of a new class of prostaglandin transporter inhibitors and characterization of their biological effects on prostaglandin E₂ transport

Prostaglandins (PGs) are involved in several major signaling pathways. Their effects are terminated when they are transported across cell membranes and oxidized intracellularly. The transport step of PG metabolism is carried out by the prostaglandin transporter (PGT). Inhibition of PGT would therefore be expected to change local or circulating concentrations of prostaglandins, and thus their biological effects. To develop PGT-specific inhibitors with high affinity, we designed a library of triazine compounds and screened 1842 small molecules by using Madin-Darby canine kidney cells stably expressing rat PGT. We found several effective PGT inhibitors. Among them, the most potent inhibitor had a K_i of 3.7 ± 0.2 μM. These inhibitors allowed us to isolate the efflux process of PGE₂ and to demonstrate that PGT does not transport PGE₂ outwardly under physiological conditions.