title: Essential role of the electroneutral Na+-HCO3- cotransporter NBCn1 in murine duodenal acid-base balance and colonic mucus layer build-up in vivo.
abstract: Duodenal epithelial cells need efficient defence strategies during gastric acidification of the lumen, while colonic mucosa counteracts damage by pathogens by building up a bacteria-free adherent mucus layer. Transport of HCO3(-) is considered crucial for duodenal defence against acid as well as for mucus release and expansion, but the transport pathways involved are incompletely understood. This study investigated the significance of the electroneutral Na(+)-HCO3(-) cotransporter NBCn1 for duodenal defence against acid and colonic mucus release. NBCn1 was localized to the basolateral membrane of duodenal villous enterocytes and of colonic crypt cells, with predominant expression in goblet cells. Duodenal villous enterocyte intracellular pH was studied before and during a luminal acid load by two-photon microscopy in exteriorized, vascularly perfused, indicator (SNARF-1 AM)-loaded duodenum of isoflurane-anaesthetized, systemic acid-base-controlled mice. Acid-induced HCO3(-) secretion was measured in vivo by single-pass perfusion and pH-stat titration. After a luminal acid load, NBCn1-deficient duodenocytes were unable to recover rapidly from intracellular acidification and could not respond adequately with protective HCO3(-) secretion. In the colon, build-up of the mucus layer was delayed, and a decreased thickness of the adherent mucus layer was observed, suggesting that basolateral HCO3(-) uptake is essential for optimal release of mucus. The electroneutral Na(+)-HCO3(-) cotransporter NBCn1 displays a differential cellular distribution in the murine intestine and is essential for HCO3(-)-dependent mucosal protective functions, such as recovery of intracellular pH and HCO3(-) secretion in the duodenum and secretion of mucus in the colon.
authors: Department of Gastroenterology, Hannover Medical School, Hannover, Germany.
authors: Anurag Kumar
authors: AK
authors: Singh
authors: Weiliang
authors: W
authors: Xia
authors: Brigitte
authors: B
authors: Riederer
authors: Marina
authors: M
authors: Juric
authors: Junhua
authors: J
authors: Li
authors: Wen
authors: W
authors: Zheng
authors: Ayhan
authors: A
authors: Cinar
authors: Fang
authors: F
authors: Xiao
authors: Oliver
authors: O
authors: Bachmann
authors: Penghong
authors: P
authors: Song
authors: Jeppe
authors: J
authors: Praetorius
authors: Christian
authors: C
authors: Aalkjaer
authors: Ursula
authors: U
authors: Seidler
mesh_terms: D000136:Acid-Base Equilibrium; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D003106:Colon / Q000378:metabolism*; D004386:Duodenum / Q000378:metabolism*; D005260:Female; D006863:Hydrogen-Ion Concentration; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009093:Mucus / Q000378:metabolism*; D027982:Sodium-Bicarbonate Symporters / Q000502:physiology*
chemical_list: D001639:Bicarbonates; C498904:Slc4a7 protein, mouse; D027982:Sodium-Bicarbonate Symporters
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