Dual role of CFTR in cAMP-stimulated HCO3- secretion across murine duodenum

被引:124
作者
Clarke, LL
Harline, MC
机构
[1] Univ Missouri, Dalton Cardiovasc Res Ctr 324D, Columbia, MO 65211 USA
[2] Univ Missouri, Dept Vet Biomed Sci, Columbia, MO 65211 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY | 1998年 / 274卷 / 04期
关键词
cystic fibrosis; cystic fibrosis transmembrane conductance regulator; chloride secretion; chloride/bicarbonate exchanger; anion exchanger; pH stat;
D O I
10.1152/ajpgi.1998.274.4.G718
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
The role of the cystic fibrosis transmembrane conductance regulator (CFTR) in cAMP-stimulated HCO3- secretion across the murine duodenum was investigated. Serosal-to-mucosal flux of HCO3- (J(s-->m) in mu eq.cm(-2).h(-1)) and short-circuit current (I-sc; in mu eq.cm(-2).h(-1)) were measured by the pH stat method in duodenum from CFTR knockout [CFTR(-)] and normal [CFTR(+)] mice. Under control conditions, forskolin increased J(s-->m) and I-sc (+1.7 and +3.5, respectively) across the CFTR(+) but not CFTR(-) duodenum. Both the forskolin-stimulated Delta J(s-->m) and Delta I-sc were abolished by the CFTR channel blocker 5-nitro-2-(3-phenylpropylamino)benzoate, whereas inhibition of luminal Cl-/HCO3- exchange by luminal Cl- removal or DIDS reduced the J(s-->m) by similar to 18% without a consistent effect on the Delta I-sc. Methazolamide also reduced the J(s-->m) by 39% but did not affect the Delta I-sc. When carbonic anhydrase-dependent HCO3- secretion was isolated by using a CO2-gassed, HCO3- free Ringer bath, forskolin stimulated the J(s-->m) and I-sc (+0.7 and +2.0; respectively) across CFTR(+) but not CFTR(-) duodenum. Under these conditions, luminal Cl- substitution or DIDS abolished the J(s-->m) but not the Delta I-sc. It was concluded that cAMP-stimulated HCO3- secretion across the duodenum involves 1) electrogenic secretion via a CFTR HCO3- conductance and 2) electroneutral secretion via a CFTR-dependent Cl-/HCO3- exchange process that is closely associated with the carbonic anhydrase activity of the epithelium.
引用
收藏
页码:G718 / G726
页数:9
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