{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T06:36:57Z","timestamp":1791009417014,"version":"4.1.0"},"reference-count":52,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2010,4]]},"abstract":"<jats:p>Anion secretion by colonic epithelium is dependent on apical CFTR-mediated anion conductance and basolateral ion transport. In many tissues, the NKCC1 Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-2Cl<jats:sup>\u2212<\/jats:sup>cotransporter mediates basolateral Cl<jats:sup>\u2212<\/jats:sup>uptake. However, additional evidence suggests that the AE2 Cl<jats:sup>\u2212<\/jats:sup>\/HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>exchanger, when coupled with the NHE1 Na<jats:sup>+<\/jats:sup>\/H<jats:sup>+<\/jats:sup>exchanger or a Na<jats:sup>+<\/jats:sup>-HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>cotransporter (NBC), contributes to HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>and\/or Cl<jats:sup>\u2212<\/jats:sup>uptake. To analyze the secretory functions of AE2 in proximal colon, short-circuit current ( I<jats:sub>sc<\/jats:sub>) responses to cAMP and inhibitors of basolateral anion transporters were measured in muscle-stripped wild-type (WT) and AE2-null (AE2<jats:sup>\u2212\/\u2212<\/jats:sup>) proximal colon. In physiological Ringer, the magnitude of cAMP-stimulated I<jats:sub>sc<\/jats:sub>was the same in WT and AE2<jats:sup>\u2212\/\u2212<\/jats:sup>colon. However, the I<jats:sub>sc<\/jats:sub>response in AE2<jats:sup>\u2212\/\u2212<\/jats:sup>colon exhibited increased sensitivity to the NKCC1 inhibitor bumetanide and decreased sensitivity to the distilbene derivative SITS (which inhibits AE2 and some NBCs), indicating that loss of AE2 results in a switch to increased NKCC1-supported anion secretion. Removal of HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>resulted in robust cAMP-stimulated I<jats:sub>sc<\/jats:sub>in both AE2<jats:sup>\u2212\/\u2212<\/jats:sup>and WT colon that was largely mediated by NKCC1, whereas removal of Cl<jats:sup>\u2212<\/jats:sup>resulted in sharply decreased cAMP-stimulated I<jats:sub>sc<\/jats:sub>in AE2<jats:sup>\u2212\/\u2212<\/jats:sup>colon relative to WT controls. Inhibition of NHE1 had no effect on cAMP-stimulated I<jats:sub>sc<\/jats:sub>in AE2<jats:sup>\u2212\/\u2212<\/jats:sup>colon but caused a switch to NKCC1-supported secretion in WT colon. Thus, in AE2<jats:sup>\u2212\/\u2212<\/jats:sup>colon, Cl<jats:sup>\u2212<\/jats:sup>secretion supported by basolateral NKCC1 is enhanced, whereas HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>secretion is diminished. These results show that AE2 is a component of the basolateral ion transport mechanisms that support anion secretion in the proximal colon.<\/jats:p>","DOI":"10.1152\/ajpgi.00178.2009","type":"journal-article","created":{"date-parts":[[2010,1,29]],"date-time":"2010-01-29T03:19:38Z","timestamp":1264735178000},"page":"G493-G503","source":"Crossref","is-referenced-by-count":36,"title":["AE2 Cl<sup>\u2212<\/sup>\/HCO<sub>3<\/sub><sup>\u2212<\/sup>exchanger is required for normal cAMP-stimulated anion secretion in murine proximal colon"],"prefix":"10.1152","volume":"298","author":[{"given":"Lara R.","family":"Gawenis","sequence":"first","affiliation":[{"name":"Department of Physiology, University of Utah, Salt Lake City, Utah;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily M.","family":"Bradford","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, Cincinnati, 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