Cftr mediates camp- and ca2+-activated duodenal epithelial hco3-
secretion.
Hogan, Daniel L., Diane L. Crombie, Jon I. Isenberg, Per Svendsen, Ove
B. Schaffalitzky De Muckadell, and Mark A. Ainsworth.
Biomedical Laboratory and Department of Medical Gastroenterology,
Odense University, Denmark, and Division of Gastroenterology, UCSD
Medical Center, San Diego, CA, USA
APStracts 3:0226G, 1996.
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 (cftrm1UNC), normal
[CFTR(+/+)] littermates (34-46d) were compared to CFTR(-/-) (34-39d).
Anesthesia was induced and maintained with hypnorm/midazolam i.p. The
proximal duodenum (4-7mm) was canulated and perfused with 154 mM
NaCl. Either forskolin (10-6-10-4M) or carbachol (10-6-10-3M) was
perfused intraluminally to activate 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(+/+),
2.8 +/- 0.5 vs. 5.3 +/- 0.4 [mu]mol/cm-h. Moreover, in CFTR(-/-),
both forskolin- and carbachol-stimulated peak HCO3- secretion were 4
-fold less compared to CFTR(+/+) littermates [3.7 +/- 0.2 vs. 15.6 +/-
2.1 and 4.7 +/- 0.3 vs. 14.2 +/- 2.5 [mu]mol/cm-h, respectively (P
< 0.01)]. In conclusion, CFTR plays a significant role in
mediating basal, cAMP- and Ca2+-activated duodenal epithelial HCO3-
secretion.
Received 24 April 1996; accepted in final form 10 October 1996.
APS Manuscript Number G154-6.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996