2007 Fiscal Year Final Research Report Summary
Role of a novel prostaglandin transporter OAT-PG in sodium transport regulation mechanism
| Project/Area Number |
18590900
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | Kyorin University |
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Principal Investigator |
ANZAI Naohiko Kyorin University, Sch. of Med. Dept. of Pharmacol. and Toxicol, Lecturer (70276054)
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| Co-Investigator(Kenkyū-buntansha) |
KANAI Yoshikatsu Kyorin Univ., Sch. of Med. Dept. of Pharmacol. and Toxicol, Professor (60204533)
HIRATA Taku Kyorin Univ., Sch. of Med. Dept. of Pharmacol. and Toxicol, Assistant Professor (60372918)
FUKUTOMI Toshiyuki Kyorin Univ., Sch. of Med. Dept. of Pharmacol. and Toxicol, Assistant Professor (30439187)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Prostaglandin / Kidney / Cyclooxigenase / Anions / Transporter / COX-2 / PDZ / PDZ proteins |
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| Research Abstract |
In the kidney, prostaglandins (PGs), especially prostaglandin E_2(PGE_2), have important roles in renal hemodynamics, renin release, tubular sodium and water reabsorption. Because PGs are charged organic anions at physiological pH, they poorly penetrate biological membranes. Accordingly, PG transport is a carrie瀕ediated process. So far only prostaglandin transporter (PGT) from OATP (SLC0/SLC21) family is known as a transporter specific to PGs. Recently, we isolated a cDNA encoding a novel prostaglandin-specific transporter from mouse kidney. Because this transporter belongs to organic anion transporter (OAT) family (SLC22) structurally distinct from PGT, we named this prostaglandin-specific organic anion transporter (OAT-PG). OAT-PG specifically mediated a transport of PGs such as PGE_2 and PGF_<2a>. It was speculated that OAT-PG plays an important role in renal handling of PGE_2 and contributes to physiological functions involving in PGE_2 metabolism. Particularly, through the interac
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tion with COX-2 and EP4 receptor, PGE_2 may function as a signaling molecule that regulates the sodium transport at the distal segments of nephron.
This study was performed to examine the possibility that OAT-PG constitute the renal apical prostaglandin signaling mechanism. First, we investigate the driving force of OAT-PG-mediated PGs transport because in in vitro PG transport via OAT-PG seems bidirectional By using trans-stimulatory experiments, we identified that inorganic sulfate ion may be a counter ion for OATPG-mediated PGs transport. Next, to confirm that the components of renal apical PG signaling such as OATPG, COX-2and EP4 are tethered by some kind of scaffolding protein (s), we perfomed the yeast two-hybrid screening of kidney cDNA library using OATPG C-terminal sequence as bait. From this screening, we succeeded to identify that multivalent PDZ-domain protein CIPP (Channel-Interacting PDZ protein) is the binding partner of OAT-PG. These results will contribute to the clarification of renal apical PG signaling mechanism surrounding OAT-PG. Less
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[Journal Article] Functional and immunochemical characterization of a novel organic anion transporter Oat8 (Slc22a9) in rat renal collecting duct.2008
Author(s)
Yokoyama H, Anzai N. Ljubojevic M, Ohtsu N, Sakata T, Miyazaki H, Nonoguchi H, Islam R, Onozato M, Tojo A, Tomita K, Kanai Y, Igarashi T, Sabolic I, Endou H.
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Journal Title
Cell Physiol Biochem. 21
Pages: 269-278
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Sodium-hydrogen exchanger regulatory factor-1 interacts with mouse urate transporter 1 to regulate renal proximal tubule uric acid transport.2007
Author(s)
Cunningham R, Brazie M, Kanumuru S, E X, Biswas R, Wang F, Steplock D, Wade JB, Anzai N. Endou H, Shenolikar S, Weinman EJ.
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Journal Title
J Am Soc Nephrol. 18
Pages: 1419-1425
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Role of mouse organic anion transporter 3 (m0at3) as a basolateral prostaglandin E2 transport pathway.2007
Author(s)
Nilwarangkoon S, Anzai N. Shiraya K, Yu E, Islam R, Cha SH, Onozato ML, Miura D, Jutabha P, Tojo A, Kanai Y, Endou H.
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Journal Title
J Pharmacol Sci. 103
Pages: 48-55
Description
「研究成果報告書概要(欧文)」より
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