{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T20:38:48Z","timestamp":1778272728067,"version":"3.51.4"},"reference-count":48,"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":[[2007,1]]},"abstract":"<jats:p>P2Y receptors couple to G proteins and either mobilize intracellular Ca<jats:sup>2+<\/jats:sup>or alter cAMP levels to modulate the activity of Ca<jats:sup>2+<\/jats:sup>- and cAMP-sensitive ion channels. We hypothesize that increased ion transport into the lumen of MDCK cysts can osmotically drive fluid movement and increase cyst size. Furthermore, activation of the adenylate cyclase\/cAMP pathway may trigger cell proliferation via an extracellular signal-related kinase cascade. To test this hypothesis, several P2Y receptor inhibitors were used on the MDCK in vitro model of renal cyst formation. The nonspecific P2 receptor inhibitors reactive blue 2 and suramin reduced cyst growth significantly, as did PPADS and, to a lesser extent, the P2Y<jats:sub>1<\/jats:sub>-specific antagonist MRS2179. Cyst growth was reduced by \u223c50% when ATP was removed from the culture medium with apyrase, although stable analogs of ATP failed to increase cyst size. The nonselective P2X receptor inhibitor Coomassie brilliant blue G was ineffective at reducing cyst growth, suggesting no involvement of P2X receptors. Finally, the presence of selective inhibitors of ERK activation (either PD98059 or U0126) greatly reduced cyst growth, whereas in untreated cysts ERK activity was observed to increase with time. We conclude that stimulation of endogenous P2Y receptors by extracellular ATP increases growth of MDCK cysts via cAMP-dependent activation of the ERK pathway. P2Y receptor antagonists may have therapeutic potential in reducing cyst size and slowing disease progression; although further studies in vitro and in vivo are needed to investigate the specificity and role of these P2Y receptors in renal cystic diseases.<\/jats:p>","DOI":"10.1152\/ajprenal.00103.2006","type":"journal-article","created":{"date-parts":[[2006,7,19]],"date-time":"2006-07-19T00:59:40Z","timestamp":1153270780000},"page":"F15-F25","source":"Crossref","is-referenced-by-count":37,"title":["Antagonism of endogenous putative P2Y receptors reduces the growth of MDCK-derived cysts cultured in vitro"],"prefix":"10.1152","volume":"292","author":[{"given":"Clare M.","family":"Turner","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian F.","family":"King","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaila S.","family":"Srai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert J.","family":"Unwin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2005.094375"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2000.00361.x"},{"key":"R3","unstructured":"Bailey MA, Imbert-Teboul M, Turner C, Srai SK, Burnstock G, Unwin RJ.Evidence for basolateral P2Y6receptors along the rat proximal tubule: functional and molecular characterization.J Am Soc Nephrol12: 1640\u20131647, 2001."},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M410013200"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1124\/mol.63.6.1407"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1007\/s00232-001-0141-y"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00386.2002"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1016\/S0898-6568(00)00083-8"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1997.503bb.x"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1989.137"},{"key":"R11","doi-asserted-by":"crossref","unstructured":"Hanaoka K, Guggino WB.cAMP regulates cell proliferation and cyst formation in autosomal polycystic kidney disease cells.J Am Soc Nephrol11: 1179\u20131187, 2000.","DOI":"10.1681\/ASN.V1171179"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.1.346"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1042\/cs1040217"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1124\/mol.58.1.82"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00293.2000"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00020.2004"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.15.6007"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1995.269.3.F381"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1042\/bj3220259"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2003.00755.x"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-11-04211.1999"},{"key":"R22","doi-asserted-by":"crossref","unstructured":"North RA.Molecular physiology of P2X receptors.Physiol Rev1013\u20131067, 2002.","DOI":"10.1152\/physrev.00015.2002"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1007\/s002329900599"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/15.6.747"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.36.23093"},{"key":"R26","doi-asserted-by":"crossref","unstructured":"Ralevic V, Burnstock G.Receptors for purines and pyrimidines.Pharmacol Rev50: 413\u2013492, 1998.","DOI":"10.1016\/S0031-6997(24)01373-5"},{"key":"R27","doi-asserted-by":"publisher","DOI":"10.1111\/j.1743-3150.2004.00477.x"},{"key":"R28","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.81.3.635"},{"key":"R29","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.1.59"},{"key":"R30","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.2001.280.6.F945"},{"key":"R31","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.0337.2000"},{"key":"R32","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2736(81)90329-1"},{"key":"R33","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1991.sp018394"},{"key":"R34","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.1041510215"},{"key":"R35","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110352200"},{"key":"R36","doi-asserted-by":"publisher","DOI":"10.1159\/000082247"},{"key":"R37","doi-asserted-by":"publisher","DOI":"10.1159\/000073754"},{"key":"R38","doi-asserted-by":"publisher","DOI":"10.1042\/bj3310863"},{"key":"R39","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1999.9558"},{"key":"R40","doi-asserted-by":"publisher","DOI":"10.1007\/s002100000310"},{"key":"R41","doi-asserted-by":"crossref","unstructured":"Wildman SS, Hooper KM, Turner CM, Sham JS, Lakatta EG, King BF, Unwin RJ, Sutters M.The isolated polycystin-1 cytoplasmic COOH terminus prolongs ATP-stimulated Cl\u2212conductance through increased Ca2+entry.Am J Physiol Renal Physiol285: F1168\u2013F1178, 2003.","DOI":"10.1152\/ajprenal.00171.2003"},{"key":"R42","doi-asserted-by":"crossref","unstructured":"Wildman SS, Unwin RJ, King BF.Extended pharmacological profiles of rat P2Y2 and rat P2Y4 receptors and their sensitivity to extracellular H+and Zn2+ions.Br J Pharmacol2003.","DOI":"10.1038\/sj.bjp.0705544"},{"key":"R43","doi-asserted-by":"crossref","unstructured":"Wilson PD, Hovater JS, Casey CC, Fortenberry JA, Schwiebert EM.ATP release mechanisms in primary cultures of epithelia derived from the cysts of polycystic kidneys.J Am Soc Nephrol10: 218\u2013229, 1999.","DOI":"10.1681\/ASN.V102218"},{"key":"R44","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2003.00023.x"},{"key":"R45","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2000.00991.x"},{"key":"R46","doi-asserted-by":"publisher","DOI":"10.1007\/PL00005015"},{"key":"R47","unstructured":"Zambon AC, Hughes RJ, Meszaros JG, Wu JJ, Torres B, Brunton LL, Insel PA.P2Y2receptor of MDCK cells: cloning, expression, and cell-specific signaling.Am J Physiol Renal Physiol279: F1045\u2013F1052, 2000."},{"key":"R48","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1995.tb13312.x"}],"container-title":["American Journal of Physiology-Renal Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajprenal.00103.2006","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T23:55:14Z","timestamp":1736466914000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajprenal.00103.2006"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,1]]},"references-count":48,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2007,1]]}},"alternative-id":["10.1152\/ajprenal.00103.2006"],"URL":"https:\/\/doi.org\/10.1152\/ajprenal.00103.2006","relation":{},"ISSN":["1931-857X","1522-1466"],"issn-type":[{"value":"1931-857X","type":"print"},{"value":"1522-1466","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,1]]}}}