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Here, we determined the effect of graded concentrations of tolvaptan on intracellular cAMP, ERK activity, cell proliferation, and transcellular Cl<jats:sup>\u2212<\/jats:sup>secretion using human ADPKD cyst epithelial cells. Incubation of ADPKD cells with 10<jats:sup>\u22129<\/jats:sup>M AVP increased intracellular cAMP and stimulated ERK and cell proliferation. Tolvaptan caused a concentration-dependent inhibition of AVP-induced cAMP production with an apparent IC<jats:sub>50<\/jats:sub>of \u223c10<jats:sup>\u221210<\/jats:sup>M. Correspondingly, tolvaptan inhibited AVP-induced ERK signaling and cell proliferation. Basolateral application of AVP to ADPKD cell monolayers grown on permeable supports caused a sustained increase in short-circuit current that was completely blocked by the Cl<jats:sup>\u2212<\/jats:sup>channel blocker CFTR<jats:sub>inh-172<\/jats:sub>, consistent with AVP-induced transepithelial Cl<jats:sup>\u2212<\/jats:sup>secretion. Tolvaptan inhibited AVP-induced Cl<jats:sup>\u2212<\/jats:sup>secretion and decreased in vitro cyst growth of ADPKD cells cultured within a three-dimensional collagen matrix. These data demonstrate that relatively low concentrations of tolvaptan inhibit AVP-stimulated cell proliferation and Cl<jats:sup>\u2212<\/jats:sup>-dependent fluid secretion by human ADPKD cystic cells.<\/jats:p>","DOI":"10.1152\/ajprenal.00243.2011","type":"journal-article","created":{"date-parts":[[2011,8,4]],"date-time":"2011-08-04T04:24:58Z","timestamp":1312431898000},"page":"F1005-F1013","source":"Crossref","is-referenced-by-count":152,"title":["Tolvaptan inhibits ERK-dependent cell proliferation, Cl<sup>\u2212<\/sup>secretion, and in vitro cyst growth of human ADPKD cells stimulated by vasopressin"],"prefix":"10.1152","volume":"301","author":[{"given":"Gail A.","family":"Reif","sequence":"first","affiliation":[{"name":"Departments of 1Medicine,"},{"name":"The Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamio","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"The 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