Na+/HCO3- cotransport in normal and cystic fibrosis intestine.
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.
Seidler
U
U
1st Department of Medicine, University of Tübingen, Tübingen, Germany. ursula.seidler@uni-tuebingen.de
Bachmann
O
O
Jacob
P
P
Christiani
S
S
Blumenstein
I
I
Rossmann
H
H
D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D003106:Colon / Q000737:chemistry / Q000502:physiology / Q000503:physiopathology; D003550:Cystic Fibrosis / Q000503:physiopathology*; D004386:Duodenum / Q000737:chemistry / Q000502:physiology / Q000503:physiopathology; D006801:Humans; D007422:Intestines / Q000737:chemistry / Q000502:physiology / Q000503:physiopathology*; D011817:Rabbits; D027982:Sodium-Bicarbonate Symporters / Q000096:biosynthesis / Q000502:physiology*; D017923:Sodium-Hydrogen Exchangers / Q000096:biosynthesis / Q000502:physiology; D028021:Sodium-Potassium-Chloride Symporters / Q000096:biosynthesis / Q000502:physiology
D001639:Bicarbonates; D027982:Sodium-Bicarbonate Symporters; D017923:Sodium-Hydrogen Exchangers; D028021:Sodium-Potassium-Chloride Symporters