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We and others have demonstrated in human ADPKD cyst cells the absence of flow-induced Ca<jats:sub>i<\/jats:sub><jats:sup>2+<\/jats:sup>signaling exhibited by normal renal epithelial cells. We now extend these findings to primary and telomerase-immortalized normal and ADPKD epithelial cells of different genotype and of both proximal and distal origins. Flow-induced elevation of Ca<jats:sub>i<\/jats:sub><jats:sup>2+<\/jats:sup>concentration ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>) was absent from ADPKD cyst cells, but in normal cells was mediated by flow-sensitive ATP release and paracrine P2R activation, modulated by ecto-nucleotidase activity, and abrogated by P2R inhibition or extracellular ATP hydrolysis. In contrast to the elevated ATP release from ADPKD cells in static isotonic conditions or in hypotonic conditions, flow-induced ATP release from cyst cells was lower than from normal cells. Extracellular ATP rapidly reduced thapsigargin-elevated [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>in both ADPKD cyst and normal cells, but cyst cells lacked the subsequent, slow, oxidized ATP-sensitive [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>recovery present in normal cells. Telomerase-immortalized cyst cells also exhibited altered CD39 and P2X7 mRNA levels. Thus the loss of flow-induced, P2R-mediated Ca<jats:sub>i<\/jats:sub><jats:sup>2+<\/jats:sup>signaling in human ADPKD cyst epithelial cells was accompanied by reduced flow-sensitive ATP release, altered purinergic regulation of store-operated Ca<jats:sup>2+<\/jats:sup>entry, and altered expression of gene products controlling extracellular nucleotide signaling.<\/jats:p>","DOI":"10.1152\/ajprenal.90542.2008","type":"journal-article","created":{"date-parts":[[2009,2,26]],"date-time":"2009-02-26T02:27:58Z","timestamp":1235615278000},"page":"F1464-F1476","source":"Crossref","is-referenced-by-count":74,"title":["Attenuated, flow-induced ATP release contributes to absence of flow-sensitive, purinergic Ca<sub>i<\/sub><sup>2+<\/sup>signaling in human ADPKD cyst epithelial cells"],"prefix":"10.1152","volume":"296","author":[{"given":"Chang","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris 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