{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T04:53:16Z","timestamp":1745470396587,"version":"3.40.4"},"reference-count":13,"publisher":"S. Karger AG","issue":"2","license":[{"start":{"date-parts":[[2008,10,13]],"date-time":"2008-10-13T00:00:00Z","timestamp":1223856000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2008,10,13]],"date-time":"2008-10-13T00:00:00Z","timestamp":1223856000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nephron Physiol"],"abstract":"<i>Background\/Aims:<\/i> We have previously reported that a complex of cadmium-metallothionein (Cd-MT) directly affects the apical Na-glucose cotransporter on the luminal side in proximal tubules, suggesting that Cd-MT is more toxic than CdCl<sub>2<\/sub> in causing tubulopathy. To find the potential mechanisms, we evaluated the effect of luminal pH alteration and carbonic anhydrase (CA) inhibition on Cd-MT-induced reduction of glucose-dependent transmural voltage in rabbit S2 segments perfused in vitro. <i>Methods:<\/i> Before and after the addition of Cd-MT (1 \u00b5g Cd\/ml) to the lumen, the deflections of transmural voltage upon the elimination of glucose from the perfusate (\u0394Vt<sub>glu<\/sub>) were measured as a parameter of activity of the Na-glucose cotransporter. <i>Results:<\/i> During perfusion with a control solution of pH 7.4, the \u0394Vt<sub>glu<\/sub> significantly decreased after addition of Cd-MT for 10 min. A reduction in pH to 6.8 significantly shortened the time needed to reduce the \u0394Vt<sub>glu<\/sub> to <5 min, whereas an increase of pH to 7.7 significantly prolonged the time to >20 min. Furthermore, simultaneous addition of acetazolamide with control perfusate prevented the reduction. <i>P<\/i>-Fluorobenzyl-aminobenzolamide (pFB-ABZ), a membrane-impermeable CA inhibitor, added to the lumen also completely prevented the reduction in \u0394Vt<sub>glu<\/sub>. In rabbits with chronic Cd exposure, acetazolamide prevented the glucosuria. <i>Conclusion:<\/i> Cd-MT-induced inhibition of Na-glucose cotransporter activity in the S2 segment strongly depends on luminal pH, and that an increase in pH by inhibition of luminal membrane-bound CA is useful to prevent renal Cd toxicity.<\/jats:p>","DOI":"10.1159\/000161986","type":"journal-article","created":{"date-parts":[[2008,10,13]],"date-time":"2008-10-13T12:37:22Z","timestamp":1223901442000},"page":"p11-p20","source":"Crossref","is-referenced-by-count":2,"title":["Mechanism of Cd-Induced Inhibition of Na-Glucose Cotransporter in Rabbit Proximal Tubule Cells: Roles of Luminal pH and Membrane-Bound Carbonic Anhydrase"],"prefix":"10.1159","volume":"110","author":[{"given":"Shuichi","family":"Tsuruoka","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erik R.","family":"Swenson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akio","family":"Fujimura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masashi","family":"Imai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2008,10,13]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1002%2F%28SICI%291520-670X%281998%2911%3A2%2F3%3C275%3A%3AAID-JTRA16%3E3.0.CO%3B2-O"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1172%2FJCI116780"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1124%2Fjpet.102.048207"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1016%2F0005-2736%2872%2990327-6"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1016%2FS0300-483X%2898%2900083-3"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1046%2Fj.1523-1755.2000.00022.x"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1046%2Fj.1523-1755.2002.00371.x"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1152%2Fajprenal.00233.2003"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1124%2Fjpet.106.102574"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1046%2Fj.1523-1755.1998.00914.x"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1159%2F000085969"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1210%2Fendo-125-2-1046"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.taap.2004.08.021"}],"container-title":["Nephron Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/161986","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/161986","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T01:01:11Z","timestamp":1745456471000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000161986"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,10,13]]},"references-count":13,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2008,11,1]]}},"URL":"https:\/\/doi.org\/10.1159\/000161986","archive":["Portico"],"relation":{},"ISSN":["1660-2137"],"issn-type":[{"type":"electronic","value":"1660-2137"}],"subject":[],"published":{"date-parts":[[2008,10,13]]}}}