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Publications (5)42.84 Total impact

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    ABSTRACT: In a search for the HCO(3)(-) supply mechanisms to the enterocyte we cloned and sequenced an intestinal subtype of the Na(+)HCO(3)(-) cotransporter isoform I (dNBC1), which turned out to be identical to the pancreatic NBC1 subtype (pNBC1). Within the intestine, we found particularly high NBC1 expression levels in the duodenum and proximal colon. Experiments with stripped rabbit duodenum in Ussing-chambers revealed that Na(+)HCO(3)(-) cotransport (NBC) and CO(2) hydration/Na(+)/H(+) exchange were equally important duodenal HCO(3)(-) supply pathways and were both upregulated during cAMP-mediated secretion. In the proximal colon, however, HCO(3)(-) secretion was low but NBC1 expression even higher than in the duodenum. Ussing-chamber experiments with an NBC-specific inhibitor revealed that NBC, coupled to basolateral Cl(-)/HCO(3)(-) exchange, was an important alternative Cl(-) supply pathway to Na(+)K(+)2Cl(-) cotransport (NKCC) during cAMP-stimulated colonic Cl(-) secretion. To investigate the functional integrity of anion uptake pathways in the absence of cystic fibrosis transmembrane conductance regulator (CFTR), we fluorometrically assessed NBC and NKCC transport rates and cell volume before and during forskolin-stimulation in isolated colonic crypts from normal and CFTR (-/-) mice. Although forskolin stimulation decreased cell volume only in normal, not in CFTR (-/-) crypts, it activated NBC and NKCC to a similar degree in both normal and CFTR (-/-) crypts. We conclude that, depending on the intestinal segment, NBC1 plays an important role in basolateral HCO(3)(-) or Cl(-) uptake. Expression and activation by cAMP is preserved in CFTR (-/-) intestine.
    JOP: Journal of the pancreas 08/2001; 2(4 Suppl):247-56.
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    ABSTRACT: HCO(3)(-) supply to the enterocyte is rate limiting for duodenal HCO(3)(-) secretion (J(HCO3-)). This study defines the molecular nature of the major HCO(3)(-) uptake pathways in rabbit duodenocytes and investigates their physiologic significance and regulation during basal and stimulated J(HCO3-). pH gradient-driven (22)Na(+) uptake into duodenal basolateral membrane vesicles was partly HCO(3)(-) dependent, stilbene sensitive, and therefore mediated by Na(+)HCO(3)(-) cotransport, and partly HCO(3)(-) independent, Hoechst 642 sensitive, and therefore mediated by the Na(+)/H(+) exchanger isoform NHE1. Semiquantitative polymerase chain reaction (PCR) revealed high duodenal expression levels for the NBC1 isoform of the Na(+)HCO(3)(-) cotransporter gene family and NHE1. Cloning and comparison of full-length rabbit with human gastrointestinal and kidney NBC1 subtype revealed a conserved protein kinase A consensus sequence in the cytoplasmic N-terminus of the gastrointestinal NBC1. Inhibition of either Na(+)HCO(3)(-) cotransport or carbonic anhydrase reduced ouabain-sensitive J(HCO3-) in in vitro rabbit duodenal mucosae by approximately 50%, but did not affect 8-Br-cAMP-induced DeltaJ(HCO3-), suggesting cAMP-mediated up-regulation of the alternative pathway. However, inhibition of both Na(+)HCO(3)(-) cotransport and either carbonic anhydrase or NHE1 strongly reduced DeltaJ(HCO3-). NBC1 and NHE1 are the major base importers in rabbit duodenocytes. Na(+)HCO(3)(-) cotransport and CO(2) hydration/Na(+)/H(+) exchange are equally important pathways for duodenal HCO(3)(-) supply and are up-regulated during cAMP-mediated stimulation.
    Gastroenterology 08/2000; 119(2):406-19. · 12.82 Impact Factor
  • Stephanie Christiani, Michael Walter, Michael Gregor, Ursula Seidler
    Gastroenterology 04/2000; 118(4). · 12.82 Impact Factor
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    ABSTRACT: The stomach, duodenum, colon, and pancreas secrete HCO3- ions into the lumen. Although the importance of HCO3- secretion for the maintenance of mucosal integrity, a normal digestion, and the reabsorption of Cl- has been well established, the molecular nature of the apical and basolateral HCO3- transporting proteins has remained largely unknown. Functional studies have suggested that a Na+HCO3- cotransport system, similar but not identical to the well-characterized Na+HCO3- cotransporter in the basolateral membrane of the kidney proximal tubule, is present in duodenal and colonic enterocytes, pancreatic ducts cells, and gastric cells and involved in HCO3- uptake from the interstitium. This report describes our work towards understanding the molecular nature, cellular origin, and functional relevance of the Na+HCO3- cotransporter(s) in the stomach and intestine and reviews work by others on the function and localization of Na+HCO3- cotransport processes in the gastrointestinal tract.
    Annals of the New York Academy of Sciences 02/2000; 915:1-14. · 4.38 Impact Factor
  • Gastroenterology 01/2000; 118(4). · 12.82 Impact Factor