A novel transporter of SLC22 family specifically transports prostaglandins and co-localizes with 15-hydroxyprostaglandin dehydrogenase in renal proximal tubules

Katsuko Shiraya, Taku Hirata, Ryo Hatano, Shushi Nagamori, Pattama Wiriyasermkul, Promsuk Jutabha, Mitsunobu Matsubara, Shigeaki Muto, Hidekazu Tanaka, Shinji Asano, Naohiko Anzai, Hitoshi Endou, Akira Yamada, Hiroyuki Sakurai, Yoshikatsu Kanai

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29 Citations (Scopus)

Abstract

We identified a novel prostaglandin (PG)-specific organic anion transporter (OAT) in the OAT group of the SLC22 family. The transporter designated OAT-PG from mouse kidney exhibited Na+-independent and saturable transport of PGE2 when expressed in a proximal tubule cell line (S 2). Unusual for OAT members, OAT-PG showed narrow substrate selectivity and high affinity for a specific subset of PGs, including PGE 2, PGF, and PGD2. Similar to PGE 2 receptor and PGT, a structurally distinct PG transporter, OAT-PG requires for its substrates an α-carboxyl group, with a double bond between C13 and C14 as well as a (S)-hydroxyl group at C15. Unlike the PGE 2 receptor, however, the hydroxyl group at C11 in a cyclopentane ring is not essential for OAT-PG substrates. Addition of a hydroxyl group at C19 or C20 impairs the interaction with OAT-PG, whereas an ethyl group at C20 enhances the interaction, suggesting the importance of hydrophobicity around the ω-tail tip forming a "hydrophobic core" accompanied by a negative charge, which is essential for substrates of OAT members. OAT-PG-mediated transport is concentrative in nature, although OAT-PG mediates both facilitative and exchange transport. OAT-PG is kidney-specific and localized on the basolateral membrane of proximal tubules where a PG-inactivating enzyme, 15-hydroxyprostaglandin dehydrogenase, is expressed. Because of the fact that 15-keto-PGE2, the metabolite of PGE 2 produced by 15-hydroxyprostaglandin dehydrogenase, is not a substrate of OAT-PG, the transport-metabolism coupling would make unidirectional PGE2 transport more efficient. By removing extracellular PGE2, OAT-PG is proposed to be involved in the local PGE2 clearance and metabolism for the inactivation of PG signals in the kidney cortex.

Original languageEnglish
Pages (from-to)22141-22151
Number of pages11
JournalJournal of Biological Chemistry
Volume285
Issue number29
DOIs
Publication statusPublished - 2010 Jul 16

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Shiraya, K., Hirata, T., Hatano, R., Nagamori, S., Wiriyasermkul, P., Jutabha, P., Matsubara, M., Muto, S., Tanaka, H., Asano, S., Anzai, N., Endou, H., Yamada, A., Sakurai, H., & Kanai, Y. (2010). A novel transporter of SLC22 family specifically transports prostaglandins and co-localizes with 15-hydroxyprostaglandin dehydrogenase in renal proximal tubules. Journal of Biological Chemistry, 285(29), 22141-22151. https://doi.org/10.1074/jbc.M109.084426