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This was associated with elevated renal mPGES-1 protein expression and increased urine PGE<jats:sub>2<\/jats:sub>excretion. In contrast, mPGES-1 \u2212\/\u2212 mice were largely resistant to lithium-induced polyuria and a urine concentrating defect, accompanied by nearly complete blockade of high urine PGE<jats:sub>2<\/jats:sub>and cAMP output. Immunoblotting, immunohistochemistry, and quantitative (q) RT-PCR consistently detected a significant decrease in aquaporin-2 (AQP2) protein expression in both the renal cortex and medulla of lithium-treated +\/+ mice. This decrease was significantly attenuated in the \u2212\/\u2212 mice. qRT-PCR detected similar patterns of changes in AQP2 mRNA in the medulla but not in the cortex. Similarly, the total protein abundance of the Na-K-2Cl cotransporter (NKCC2) in the medulla but not in the cortex of the +\/+ mice was significantly reduced by lithium treatment. In contrast, the dowregulation of renal medullary NKCC2 expression was significantly attenuated in the \u2212\/\u2212 mice. We conclude that mPGES-1-derived PGE<jats:sub>2<\/jats:sub>mediates lithium-induced polyuria likely via inhibition of AQP2 and NKCC2 expression.<\/jats:p>","DOI":"10.1152\/ajprenal.00117.2009","type":"journal-article","created":{"date-parts":[[2009,8,20]],"date-time":"2009-08-20T00:59:07Z","timestamp":1250729947000},"page":"F1689-F1696","source":"Crossref","is-referenced-by-count":34,"title":["Mice lacking mPGES-1 are resistant to lithium-induced polyuria"],"prefix":"10.1152","volume":"297","author":[{"given":"Zhanjun","family":"Jia","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, University of Utah, and Veterans Affairs Medical Center, Salt Lake City, Utah"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haiping","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Utah, and Veterans Affairs Medical Center, Salt Lake City, 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