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Little is known, however, about the regulation and physiological relevance of this system. Patch\u2010clamp studies in freshly isolated ASDN provide evidence that increased dietary Na\n                    <jats:sup>+<\/jats:sup>\n                    intake in wild\u2010type mice lowers ENaC\n                    <jats:italic>P<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>o<\/jats:italic>\n                    <\/jats:sub>\n                    , consistent with a contribution to Na\n                    <jats:sup>+<\/jats:sup>\n                    homeostasis, and is associated with increased urinary concentrations of UTP and the ATP hydrolytic product, ADP. Genetic deletion of P2Y\n                    <jats:sub>2<\/jats:sub>\n                    receptors in mice (P2Y\n                    <jats:sub>2<\/jats:sub>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ; litter\u2010mates to wild\u2010type mice) or inhibition of apical P2Y\u2010receptor activation in wild\u2010type mice prevents dietary Na\n                    <jats:sup>+<\/jats:sup>\n                    \u2010induced lowering of ENaC\n                    <jats:italic>P<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>o<\/jats:italic>\n                    <\/jats:sub>\n                    . Although they lack suppression of ENaC\n                    <jats:italic>P<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>o<\/jats:italic>\n                    <\/jats:sub>\n                    by dietary NaCl, P2Y\n                    <jats:sub>2<\/jats:sub>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice do not exhibit NaCl\u2010sensitive blood pressure, perhaps as a consequence of compensatory down\u2010regulation of aldosterone levels. Consistent with this hypothesis, clamping mineralocorticoid activity at high levels unmasks greater ENaC activity and NaCl sensitivity of blood pressure in P2Y\n                    <jats:sub>2<\/jats:sub>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. The studies indicate a key role of the apical ATP\/UTP\u2010P2Y\n                    <jats:sub>2<\/jats:sub>\n                    \u2010receptor system in the inhibition of ENaC\n                    <jats:italic>P<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>o<\/jats:italic>\n                    <\/jats:sub>\n                    in the ASDN in response to an increase in Na\n                    <jats:sup>+<\/jats:sup>\n                    intake, thereby contributing to NaCl homeostasis and blood pressure regulation.\u2014Pochynyuk, O., Rieg, T., Bugaj, V., Schroth, J., Fridman, A., Boss, G. R., Insel, P. A., Stockand, J. D., Vallon, V. Dietary Na\n                    <jats:sup>+<\/jats:sup>\n                    inhibits the open probability of the epithelial sodium channel in the kidney by enhancing apical P2Y\n                    <jats:sub>2<\/jats:sub>\n                    \u2010receptor tone.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    24, 2056\u20132065 (2010).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.09-151506","type":"journal-article","created":{"date-parts":[[2010,1,22]],"date-time":"2010-01-22T22:12:50Z","timestamp":1264198370000},"page":"2056-2065","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":96,"title":["Dietary Na\n                    <sup>+<\/sup>\n                    inhibits the open probability of the epithelial sodium channel in the kidney by enhancing apical P2Y\n                    <sub>2<\/sub>\n                    \u2010receptor tone"],"prefix":"10.1096","volume":"24","author":[{"given":"Oleh","family":"Pochynyuk","sequence":"first","affiliation":[{"name":"Department of Physiology University of Texas Health Science Center San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timo","family":"Rieg","sequence":"additional","affiliation":[{"name":"Department of Medicine University of California San Diego La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladislav","family":"Bugaj","sequence":"additional","affiliation":[{"name":"Department of Physiology University of Texas Health Science Center San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana","family":"Schroth","sequence":"additional","affiliation":[{"name":"Veterans Affairs San Diego Healthcare System San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alla","family":"Fridman","sequence":"additional","affiliation":[{"name":"Department of Medicine University of California San Diego La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerry R.","family":"Boss","sequence":"additional","affiliation":[{"name":"Department of Medicine University of California San Diego La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul A.","family":"Insel","sequence":"additional","affiliation":[{"name":"Department of Medicine University of California San Diego La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James D.","family":"Stockand","sequence":"additional","affiliation":[{"name":"Department of Physiology University of Texas Health Science Center San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volker","family":"Vallon","sequence":"additional","affiliation":[{"name":"Department of Medicine University of California San Diego La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,1,22]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.19.1_Suppl.I2"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2005040450"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00241-0"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00075.2002"},{"key":"e_1_2_6_6_1","first-page":"237","article-title":"Purinergic signaling along the renal tubule: the current state of play","volume":"18","author":"Unwin R. 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