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Because previous studies excluded the role of intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    or protein kinase C, we examined whether purinergic regulation of Na\n                    <jats:sup>+<\/jats:sup>\n                    absorption occurs via hydrolysis of phospholipid such as phosphatidylinositol\u2010bisphosphates (PIP\n                    <jats:sub>2<\/jats:sub>\n                    ). Inhibition of amiloride\u2010sensitive short\u2010circuit currents (I\n                    <jats:sub>sc\u2010Amil<\/jats:sub>\n                    ) by adenine 5\u2032\u2010triphosphate (ATP) in native tracheal epithelia and M1 collecting duct cells was suppressed by binding neomycin to PIP\n                    <jats:sub>2<\/jats:sub>\n                    , and recovery from ATP inhibition was abolished by blocking phosphatidylinositol\u20104\u2010kinase or diacylglycerol kinase. Stimulation by ATP depleted PIP\n                    <jats:sub>2<\/jats:sub>\n                    from apical membranes, and PIP\n                    <jats:sub>2<\/jats:sub>\n                    co\u2010 immunoprecipitated the \u03b2 subunit of ENaC. ENaC was inhibited by ATP stimulation of P2Y\n                    <jats:sub>2<\/jats:sub>\n                    receptors in\n                    <jats:italic>Xenopus<\/jats:italic>\n                    oocytes. Mutations in the PIP\n                    <jats:sub>2<\/jats:sub>\n                    binding domain of \u03b2ENaC but not \u03b3ENaC reduced ENaC currents without affecting surface expression. Collectively, these data supply evidence for a novel and physiologically relevant regulation of ENaC in epithelial tissues. Although surface expression is controlled by its C terminus, N\u2010terminal binding of \u03b2ENaC to PIP\n                    <jats:sub>2<\/jats:sub>\n                    determines channel activity.\n                  <\/jats:p>","DOI":"10.1096\/fj.04-2314fje","type":"journal-article","created":{"date-parts":[[2004,10,25]],"date-time":"2004-10-25T20:15:01Z","timestamp":1098735301000},"page":"142-143","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":106,"title":["Purinergic inhibition of the epithelial Na\n                    <sup>+<\/sup>\n                    transport via hydrolysis of PIP\n                    <sub>2<\/sub>"],"prefix":"10.1096","volume":"19","author":[{"given":"K.","family":"Kunzelmann","sequence":"first","affiliation":[{"name":"Institut f\u00fcr Physiologie, Universit\u00e4t Regensburg Regensburg Germany"}]},{"given":"T.","family":"Bachhuber","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Physiologie, Universit\u00e4t Regensburg Regensburg Germany"}]},{"given":"R.","family":"Regeer","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology University of Queensland QLD Australia"}]},{"given":"D.","family":"Markovich","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology University of Queensland QLD Australia"}]},{"given":"J.","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology University of Queensland QLD Australia"}]},{"given":"R.","family":"Schreiber","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Physiologie, Universit\u00e4t Regensburg Regensburg Germany"}]}],"member":"311","published-online":{"date-parts":[[2004,10,25]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.150.1.213"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.63.5.1043"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.282.5391.1141"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1999.0631u.x"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2000.00077.x"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.20028562"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)36324-X"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.23.13953"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(00)76779-8"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.114.2.251"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.26.15370"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-12-04931.2003"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2736(89)90529-4"},{"key":"e_1_2_6_15_1","doi-asserted-by":"crossref","DOI":"10.1126\/stke.2001.111.re19","article-title":"The complex and intriguing lives of PIP2 with ion channels and transporters","volume":"2001","author":"Hilgemann D. 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