Prostaglandin transporter (OATP2A1/SLCO2A1) contributes to local disposition of eicosapentaenoic acid-derived PGE3.

Abstract Eicosapentaenoic acid (EPA)-derived prostaglandin E 3 (PGE 3 ) possesses an anti-inflammatory effect; however, information for transporters that regulate its peri-cellular concentration is limited. The present study, therefore, aimed to clarify transporters involved in local disposition of PGE 3 . PGE 3 uptake was assessed in HEK293 cells transfected with OATP2A1/ SLCO2A1 , OATP1B1/ SLCO1B1 , OATP2B1/ SLCO2B1 , OAT1/ SLC22A6 , OCT1/ SLC22A1 or OCT2/ SLC22A2 genes, compared with HEK293 cells transfected with plasmid vector alone (Mock). PGE 3 uptake by OATP2A1-expressing HEK293 cells (HEK/2A1) was the highest and followed by HEK/1B1, while no significantly higher uptake of PGE 3 than Mock cells was detected by other transporters. Saturation kinetics in PGE 3 uptake by HEK/2A1 estimated the K m as 7.202 ± 0.595 μM, which was 22 times higher than that of PGE 2 ( K m  = 0.331 ± 0.131 μM). Furthermore, tissue disposition of PGE 3 was examined in wild-type (WT) and Slco2a1 -deficient ( Slco2a1 −/− ) mice after oral administration of EPA ethyl ester (EPA-E) when they underwent intraperitoneal injection of endotoxin ( e.g. , lipopolysaccharide). PGE 3 concentration was significantly higher in the lung, and tended to increase in the colon, stomach, and kidney of Slco2a1 −/− , compared to WT mice. Ratio of PGE 2 metabolite 15-keto PGE 2 over PGE 2 concentration was significantly lower in the lung and colon of Slco2a1 −/− than that of WT mice, suggesting that PGE 3 metabolism is downregulated in Slco2a1 −/− mice. In conclusion, PGE 3 was found to be a substrate of OATP2A1, and local disposition of PGE 3 could be regulated by OATP2A1 at least in the lung.