{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:48:00Z","timestamp":1787017680055,"version":"build-2736575974"},"reference-count":36,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2006,7]]},"abstract":"<jats:p>Vasopressin increases urine concentration by stimulating plasma membrane accumulation of aquaporin-2 (AQP2) in collecting duct principal cells, allowing bulk water flow across the collecting duct from lumen to interstitium down an osmotic gradient. Mutations in the vasopressin type 2 receptor (V2R) cause hereditary X-linked nephrogenic diabetes insipidus (NDI), a disease characterized by excessive urination and dehydration. Recently, we showed that inhibition of endocytosis by the cholesterol-depleting drug methyl-\u03b2-cyclodextrin (m\u03b2CD) induces plasma membrane accumulation of AQP2 in transfected renal epithelial cells overexpressing epitope-tagged AQP2. Here, we asked whether m\u03b2CD could induce membrane accumulation of AQP2 in situ using the isolated, perfused kidney (IPK). By immunofluorescence and electron microscopy, we show that AQP2 was shifted from a predominantly intracellular localization to the apical membrane of principal cells following 1-h perfusion of Sprague-Dawley rat kidneys with 5 mM m\u03b2CD. Quantification of staining revealed that the intensity of AQP2 was increased from 647 \u00b1 114 (control) to 1,968 \u00b1 299 units (m\u03b2CD; P &lt; 0.001), an effect similar to that seen after perfusion with 4 nM dDAVP (1,860 \u00b1 298, P &lt; 0.001). Similar changes were observed following m\u03b2CD perfusion of kidneys from vasopressin-deficient Brattleboro rats. No effect of m\u03b2CD treatment on the basolateral distribution of AQP3 and AQP4 was detected. These data indicate that AQP2 constitutively recycles between the apical membrane and intracellular vesicles in principal cells in situ and that inducing apical AQP2 accumulation by inhibiting AQP2 endocytosis is a feasible goal for bypassing the defective V2R signaling pathway in X-linked NDI.<\/jats:p>","DOI":"10.1152\/ajprenal.00437.2005","type":"journal-article","created":{"date-parts":[[2006,1,31]],"date-time":"2006-01-31T22:43:31Z","timestamp":1138747411000},"page":"F246-F253","source":"Crossref","is-referenced-by-count":42,"title":["Methyl-\u03b2-cyclodextrin induces vasopressin-independent apical accumulation of aquaporin-2 in the isolated, perfused rat kidney"],"prefix":"10.1152","volume":"291","author":[{"given":"Leileata M.","family":"Russo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"McKee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"crossref","unstructured":"Andersson KE\n                      and Arner B.\n                      Effects of DDAVP, a synthetic analogue of vasopressin, in patients with cranial diabetes insipidus.\n                      Acta Med Scand\n                      192\n                      : 21\u201327, 1972.","DOI":"10.1111\/j.0954-6820.1972.tb04772.x"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.9.5171"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M412750200"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1172\/JCI9594"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1084\/jem.131.3.443"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00387.2002"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1007\/BF01463929"},{"key":"R8","unstructured":"Brown D\n                      and Nielsen S.\n                      Cell biology of vasopressin action. 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New York: Academic, 2001, p. 235\u2013276."},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1995.269.5.F663"},{"key":"R12A","unstructured":"Electronic Medicines Compendium.\n                      http:\/\/emc.medicines.org.uk\/emc\/assets\/c\/html\/displaydoc.asp?documentid=4217#CONTRAINDICATIONS\n                      ."},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.23.14800"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.2000.278.2.F317"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.2001.280.5.F794"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(01)00248-6"},{"key":"R17A","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200309017"},{"key":"R18","doi-asserted-by":"crossref","unstructured":"Katsura T\n                      , Gustafson CE, Ausiello DA, and Brown D.\n                      Protein kinase A phosphorylation is involved in regulated exocytosis of aquaporin-2 in transfected LLC-PK1 cells.\n                      Am J Physiol Renal Physiol\n                      272\n                      : F817\u2013F822, 1997.","DOI":"10.1152\/ajprenal.1997.272.6.F816"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1990.259.6.C920"},{"key":"R20","doi-asserted-by":"crossref","unstructured":"Lieberthal W\n                      , Stephens GW, Wolf EF, Rennke HG, Vasilevsky ML, Valeri CR, and Levinsky NG.\n                      Effect of erythrocytes on the function and morphology of the isolated perfused rat kidney.\n                      Renal Physiol\n                      10\n                      : 14\u201324, 1987.","DOI":"10.1159\/000173109"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1987.252.2.F331"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00179.2003"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000027355.41663.14"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.63.1.607"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.24.11663"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00024.2001"},{"key":"R27","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1999.276.2.F254"},{"key":"R28","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.2000.279.2.F370"},{"key":"R29","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.10.4.961"},{"key":"R30","doi-asserted-by":"publisher","DOI":"10.1007\/BF00233445"},{"key":"R31","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfh172"},{"key":"R32","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00257.2001"},{"key":"R33","doi-asserted-by":"publisher","DOI":"10.2174\/1570163043484824"},{"key":"R34","unstructured":"Tay M\n                      , Comper WD, Vassiliou P, Glasgow EF, Baker MS, and Pratt L.\n                      The inhibitory action of oxygen radical scavengers on proteinuria and glomerular heparan sulfate loss in the isolated perfused kidney.\n                      Biochem Int\n                      20\n                      : 767\u2013778, 1990."},{"key":"R35","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1995.269.6.F775"},{"key":"R36","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M207339200"}],"container-title":["American Journal of Physiology-Renal Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajprenal.00437.2005","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,8]],"date-time":"2019-09-08T19:11:09Z","timestamp":1567969869000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajprenal.00437.2005"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,7]]},"references-count":36,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2006,7]]}},"alternative-id":["10.1152\/ajprenal.00437.2005"],"URL":"https:\/\/doi.org\/10.1152\/ajprenal.00437.2005","relation":{},"ISSN":["1931-857X","1522-1466"],"issn-type":[{"value":"1931-857X","type":"print"},{"value":"1522-1466","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,7]]}}}