TY - JOUR
T1 - A novel transporter of SLC22 family specifically transports prostaglandins and co-localizes with 15-hydroxyprostaglandin dehydrogenase in renal proximal tubules
AU - Shiraya, Katsuko
AU - Hirata, Taku
AU - Hatano, Ryo
AU - Nagamori, Shushi
AU - Wiriyasermkul, Pattama
AU - Jutabha, Promsuk
AU - Matsubara, Mitsunobu
AU - Muto, Shigeaki
AU - Tanaka, Hidekazu
AU - Asano, Shinji
AU - Anzai, Naohiko
AU - Endou, Hitoshi
AU - Yamada, Akira
AU - Sakurai, Hiroyuki
AU - Kanai, Yoshikatsu
PY - 2010/7/16
Y1 - 2010/7/16
N2 - 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, PGF2α, 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.
AB - 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, PGF2α, 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.
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U2 - 10.1074/jbc.M109.084426
DO - 10.1074/jbc.M109.084426
M3 - Article
C2 - 20448048
AN - SCOPUS:77954611799
VL - 285
SP - 22141
EP - 22151
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 29
ER -