Acid-stimulated duodenal bicarbonate secretion involves a CFTR-mediated transport pathway in mice

Hogan, D. L.; Crombie, D. L.; Isenberg, J. I.; Svendsen, P.; Muckadell, OB Schaffalitzky de; Ainsworth, Mark

doi:10.1053/gast.1997.v113.pm9247473

Cited by 93 publications

(75 citation statements)

References 3 publications

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“…Strikingly, the phenotype of the pancreas, perhaps the most acknowledged organ of HCO 3 -transport, segregates well with genotypes that severely disrupt CFTR-dependent HCO 3 transport in this organ and in the sweat duct (15,17). Likewise, HCO 3 -secretion is reduced in the CF intestine (16,18,19). More-over, experimentally altering HCO 3 -secretion appeared to change mucus consistency in submucosal gland secretion in sheep, pigs, and human trachea (20).…”

Section: Introductionmentioning

confidence: 98%

Normal mouse intestinal mucus release requires cystic fibrosis transmembrane regulator–dependent bicarbonate secretion

García

Yang²,

Quinton³

2009

J. Clin. Invest.

256

239

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The mechanisms underlying mucus-associated pathologies in cystic fibrosis (CF) remain obscure. However, recent studies indicate that CF transmembrane conductance regulator (CFTR) is required for bicarbonate (HCO 3 -) transport and that HCO 3 -is critical for normal mucus formation. We therefore investigated the role of HCO 3 -in mucus secretion using mouse small intestine segments ex vivo. Basal rates of mucus release in the presence or absence of HCO 3 -were similar. However, in the absence of HCO 3 -, mucus release stimulated by either PGE 2 or 5-hydroxytryptamine (5-HT) was approximately half that stimulated by these molecules in the presence of HCO 3 -. Inhibition of HCO 3 -and fluid transport markedly reduced stimulated mucus release. However, neither absence of HCO 3 -nor inhibition of HCO 3 -transport affected fluid secretion rates, indicating that the effect of HCO 3 -removal on mucus release was not due to decreased fluid secretion. In a mouse model of CF (mice homozygous for the most common human CFTR mutation), intestinal mucus release was minimal when stimulated with either PGE 2 or 5-HT in the presence or absence of HCO 3 -. These data suggest that normal mucus release requires concurrent HCO 3 -secretion and that the characteristically aggregated mucus observed in mucin-secreting organs in individuals with CF may be a consequence of defective HCO 3 -transport.

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Section: Introductionmentioning

confidence: 98%

Normal mouse intestinal mucus release requires cystic fibrosis transmembrane regulator–dependent bicarbonate secretion

García

Yang²,

Quinton³

2009

J. Clin. Invest.

256

239

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“…Recent studies of CFTR indicate that this channel plays a major role in bicarbonate secretion (21,42,43). This channel, present in pancreatic ducts, duodenal epithelial cells, and Brunner's glands (44), is closely associated with epithelial HCO 3 -secretion.…”

Section: Figurementioning

confidence: 99%

Cellular bicarbonate protects rat duodenal mucosa from acid-induced injury

Akiba

Furukawa²,

Guth³

et al. 2001

J. Clin. Invest.

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“…THE CYSTIC FIBROSIS transmembrane conductance regulator (CFTR) is an apical membrane chloride channel critical to the regulation of fluid, chloride, and bicarbonate transport in the intestine (15,17,32,43). Mutations in the gene encoding CFTR result in the disease cystic fibrosis (CF) and are associated with the absence or dysfunction of CFTR on the apical membrane of epithelial cells, decreased cAMP-mediated fluid secretion, increased mucus viscosity, and intestinal obstruction (15).…”

mentioning

confidence: 99%

cAMP-dependent exocytosis and vesicle traffic regulate CFTR and fluid transport in rat jejunum in vivo

Ameen¹,

Marino

Salas

2003

American Journal of Physiology-Cell Physiology

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The cystic fibrosis transmembrane conductance regulator (CFTR) channel is regulated by cAMP-dependent vesicle traffic and exocytosis to the apical membrane in some cell types, but this has not been demonstrated in the intestinal crypt. The distribution of CFTR, lactase (control), and fluid secretion were determined in rat jejunum after cAMP activation in the presence of nocodazole and primaquine to disrupt vesicle traffic. CFTR and lactase were localized by immunofluorescence, and surface proteins were detected by biotinylation of enterocytes. Immunoprecipitates from biotinylated and nonbiotinylated cells were analyzed by streptavidin detection and immunoblots. Immunolocalization confirmed a cAMP-dependent shift of CFTR but not lactase from a subapical compartment to the apical surface associated with fluid secretion that was reduced in the presence of primaquine and nocodazole. Analysis of immunoblots from immunoprecipitates after biotinylation revealed a 3.8 ± 1.7-fold ( P < 0.005) increase of surface-exposed CFTR after vasoactive intestinal peptide (VIP). These measurements provide independent corroboration supporting a role for vesicle traffic in regulating CFTR and cAMP-induced fluid transport in the intestine.

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Acid-stimulated duodenal bicarbonate secretion involves a CFTR-mediated transport pathway in mice

Cited by 93 publications

References 3 publications

Normal mouse intestinal mucus release requires cystic fibrosis transmembrane regulator–dependent bicarbonate secretion

Normal mouse intestinal mucus release requires cystic fibrosis transmembrane regulator–dependent bicarbonate secretion

Cellular bicarbonate protects rat duodenal mucosa from acid-induced injury

cAMP-dependent exocytosis and vesicle traffic regulate CFTR and fluid transport in rat jejunum in vivo

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