CFTR mediates cAMP- and Ca2+-activated duodenal epithelial HCO3- secretion

被引:101
作者
Hogan, DL
Crombie, DL
Isenberg, JI
Svendsen, P
DeMuckadell, OBS
Ainsworth, MA
机构
[1] ODENSE UNIV, BIOMED LAB, DK-5230 ODENSE, DENMARK
[2] ODENSE UNIV, DEPT MED GASTROENTEROL, DK-5230 ODENSE, DENMARK
来源
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY | 1997年 / 272卷 / 04期
关键词
murine; acid/base transport; bicarbonate; conductance; cystic fibrosis transmembrane conductance regulator;
D O I
10.1152/ajpgi.1997.272.4.G872
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 duodenal alkaline secretion has not been directly examined. The aims of this series of experiments were to determine if CFTR mediates basal and stimulated duodenal epithelial HCO3- secretion. Utilizing the cystic fibrosis murine model (cftr(m1UNC)), we compared normal [CFTR(+/+)] littermates (34-46 days old) with CFTR(-/-) animals (34-39 days old). Anesthesia was induced and maintained with intraperitoneal Hypnorm-midazolam. The proximal duodenum (4-7 mm) was cannulated and perfused with 154 mM NaCl. Either forskolin (10(-6)-10(-4) M) or carbachol (10(-6)-10(-3) M) was perfused intraluminally to activate adenosine 3',5'-cyclic monophosphate (cAMP)- and Ca2+-mediated HCO3- secretion, respectively. Effluent volumes were weighed and HCO3- quantitated by back titration. Basal HCO3- secretion was diminished significantly (P < 0.01) in CFTR( -/-) vs. normal CFTR(+/+) mice (2.8 +/- 0.5 vs. 5.3 +/- 0.4 mu mol.cm(-1). h(-1)). Moreover, in CFTR(-/-) mice, both forskolin- and carbachol-stimulated peak HCO3- secretions were fourfold less compared with those in CFTR(+/+) Littermates (3.7 +/- 0.2 vs. 15.6 +/- 2.1 and 4.7 +/- 0.3 vs. 14.2 +/- 2.5 mu mol.cm(-1).h(-1), respectively; P < 0.01). In conclusion, CFTR plays a significant role in mediating basal, cAMP-, and Ca2+-activated duodenal epithelial HCO, secretion.
引用
收藏
页码:G872 / G878
页数:7
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