Cftr is required for camp inhibition of intestinal na+ absorption in a cystic fibrosis mouse model. Clarke, Lane L., and Matthew C. Harline. Dalton Cardiovascular Research Center and the Department of Veterinary Biomedical Sciences, University of Missouri-Columbia, Columbia, MO 65211
APStracts 2:0184G, 1995.
Acute cAMP stimulation of intestinal epithelium induces net transepithelial Cl- secretion and inhibits neutral coupled NaCl absorption. To investigate the role that the cystic fibrosis transmembrane conductance regulator (CFTR) plays in these events, we measured bioelectric changes and radioisotopic NaCl flux across jejunal tissues from gene-targeted cftr "knockout" mice [cftr(-/-) homozygotes] and their normal littermates [cftr(+/+) homozygotes and cftr(+/-) heterozygotes]. Prior to stimulation, the short-circuit current (Isc, an index of Cl- secretion) of the cftr( -/-) jejunum was essentially zero and significantly less than in the cftr(+/+) or (+/-) intestine. Acute cAMP stimulation had little effect on the bioelectric parameters of the cftr(-/-) intestine, but induced a marked increase of Isc and decrease of total tissue conductance in both the cftr(+/+) and (+/-) intestine. Differences in the magnitude of the cAMP-induced Isc between the cftr(+/+) and cftr(+/-) intestine were only observed when the cell-to-lumen anion concentration gradient was maximized by removal of permeant anions from the luminal bath. Radioisotope flux measurements revealed that Na+ and Cl- were absorbed equally across the cftr(-/-) jejunum under basal conditions. In cftr(+/+) and (+/-) intestine, Na+ was absorbed at a similar rate but net Cl- absorption was reduced from that in cftr(-/-) intestine by an amount approximating the Isc. Acute cAMP stimulation of the cftr(+/+) and (+/-) intestine abolished net NaCl absorption and induced electrogenic Cl- secretion. In contrast, net NaCl absorption was unchanged from the preceding flux period in the cftr(-/-) jejunum. The data suggest that CFTR not only mediates cAMP -induced transepithelial Cl- secretion but is also required for cAMP inhibition of neutral NaCl absorption in the intestine. 

Received 13 February 1995; accepted in final form 28 August 1995.
APS Manuscript Number G67-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 September 1995.