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

作者：Garcia Mary Abigail S; Yang Ning; Quinton Paul M^*

来源：Journal of Clinical Investigation, 2009, 119(9): 2613-2622.

DOI：10.1172/JCI38662

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 PGE2 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.

• 出版日期2009-9
• 单位首都医科大学