{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T13:32:55Z","timestamp":1790861575588,"version":"4.1.0"},"reference-count":44,"publisher":"American Physiological Society","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2012,4,1]]},"abstract":"<jats:p>Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-2Cl<jats:sup>\u2212<\/jats:sup>cotransporter (NKCC2)-mediated NaCl reabsorption in the thick ascending limb (TAL) is stimulated by AVP via V2 receptor\/PKA\/cAMP signaling. This process is antagonized by locally produced eicosanoids such as 20-HETE or prostaglandin E<jats:sub>2<\/jats:sub>, which are synthesized in a phospholipase A<jats:sub>2<\/jats:sub>-dependent reaction cascade. Using microarray-based gene expression analysis, we found evidence for an AVP-dependent downregulation of the calcium-independent isoform of PLA<jats:sub>2<\/jats:sub>, iPLA<jats:sub>2<\/jats:sub>\u03b2, in the outer medulla of rats. In the present study, we therefore examined the contribution of iPLA<jats:sub>2<\/jats:sub>\u03b2 to NKCC2 regulation. Immunoreactive iPLA<jats:sub>2<\/jats:sub>\u03b2 protein was detected in cultured mTAL cells as well as in the entire TAL of rodents and humans with the exception of the macula densa. Administration of the V2 receptor-selective agonist desmopressin (5 ng\/h; 3 days) to AVP-deficient diabetes insipidus rats increased outer medullary phosphorylated NKCC2 (pNKCC2) levels more than twofold in association with a marked reduction in iPLA<jats:sub>2<\/jats:sub>\u03b2 abundance (\u221265%; P &lt; 0.05), thus confirming microarray results. Inhibition of iPLA<jats:sub>2<\/jats:sub>\u03b2 in Sprague-Dawley rats with FKGK 11 (0.5 \u03bcM) or in mTAL cells with FKGK 11 (10 \u03bcM) or ( S)-bromoenol lactone (5 \u03bcM) for 1 h markedly increased pNKCC2 levels without affecting total NKCC2 expression. Collectively, these data indicate that iPLA<jats:sub>2<\/jats:sub>\u03b2 acts as an inhibitory modulator of NKCC2 activity and suggest that downregulation of iPLA<jats:sub>2<\/jats:sub>\u03b2 may be a relevant step in AVP-mediated urine concentration.<\/jats:p>","DOI":"10.1152\/ajprenal.00222.2011","type":"journal-article","created":{"date-parts":[[2012,1,6]],"date-time":"2012-01-06T00:33:18Z","timestamp":1325809998000},"page":"F865-F874","source":"Crossref","is-referenced-by-count":17,"title":["Group VIA phospholipase A<sub>2<\/sub>is a target for vasopressin signaling in the thick ascending limb"],"prefix":"10.1152","volume":"302","author":[{"given":"A.","family":"Paliege","sequence":"first","affiliation":[{"name":"Department of Anatomy, Charit\u00e9 Universit\u00e4tsmedizin-Berlin, Berlin;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Roeschel","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Charit\u00e9 Universit\u00e4tsmedizin-Berlin, Berlin;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Neymeyer","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Charit\u00e9 Universit\u00e4tsmedizin-Berlin, Berlin;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Seidel","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Charit\u00e9 Universit\u00e4tsmedizin-Berlin, Berlin;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Kahl","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Charit\u00e9 Universit\u00e4tsmedizin-Berlin, Berlin;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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