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

J Clin Invest. 2009 Sep;119(9):2613-22. doi: 10.1172/JCI38662. Epub 2009 Aug 24.


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 (HCO3-) transport and that HCO3- is critical for normal mucus formation. We therefore investigated the role of HCO3- in mucus secretion using mouse small intestine segments ex vivo. Basal rates of mucus release in the presence or absence of HCO3- were similar. However, in the absence of HCO3-, mucus release stimulated by either PGE2 or 5-hydroxytryptamine (5-HT) was approximately half that stimulated by these molecules in the presence of HCO3-. Inhibition of HCO3- and fluid transport markedly reduced stimulated mucus release. However, neither absence of HCO3- nor inhibition of HCO3- transport affected fluid secretion rates, indicating that the effect of HCO3- 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 PGE2 or 5-HT in the presence or absence of HCO3-. These data suggest that normal mucus release requires concurrent HCO3- secretion and that the characteristically aggregated mucus observed in mucin-secreting organs in individuals with CF may be a consequence of defective HCO3- transport.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / pharmacology
  • Animals
  • Bicarbonates / metabolism*
  • Bumetanide / pharmacology
  • Cystic Fibrosis / etiology
  • Cystic Fibrosis / genetics
  • Cystic Fibrosis / physiopathology
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism*
  • Dinoprostone / pharmacology
  • Humans
  • In Vitro Techniques
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / metabolism*
  • Intestine, Small / drug effects
  • Intestine, Small / metabolism
  • Ion Transport
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CFTR
  • Models, Biological
  • Mucus / metabolism*
  • Serotonin / pharmacology
  • Sodium Potassium Chloride Symporter Inhibitors
  • Sodium-Bicarbonate Symporters / antagonists & inhibitors


  • Bicarbonates
  • CFTR protein, human
  • Slc4a4 protein, mouse
  • Sodium Potassium Chloride Symporter Inhibitors
  • Sodium-Bicarbonate Symporters
  • Bumetanide
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Serotonin
  • Dinoprostone
  • 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid