Enhanced colonic Na+ absorption in cystic fibrosis mice versus normal mice.
Because there are reports that electrogenic Na+ absorption is increased in colonic epithelia of cystic fibrosis (CF) subjects, we tested whether amiloride-sensitive Na+ absorption was increased in the colonic epithelia of CF mice compared with normal mice on high- or low-Na+ diets. When mice consumed a diet high in Na+, none of the colonic regions (distal colon, proximal colon, or cecum) from either group of mice exhibited an amiloride-sensitive short-circuit current (Isc). However, when mice were placed on a low-Na+ diet for 2 wk, all three intestinal regions from the CF mice exhibited a significant response to amiloride (P < or = 0.05). In contrast, normal mice on the low-Na+ diet exhibited an amiloride-sensitive Isc that was smaller and only significant in the cecum and distal colon. Measurement of plasma aldosterone levels revealed that the CF mice on the low-Na+ diet had significantly greater aldosterone levels than similarly treated controls [8,906 +/- 1,039 (n = 14) vs. 5,243 +/- 1,410 pg/ml (n = 14), respectively]. When mice were infused with a constant dose of aldosterone (1 microg x g(-1) x day(-1)) for 7 days, the distal colon of the CF mice still had a significantly greater amiloride-sensitive Isc than did the normal distal colon. If the presence of CF transmembrane conductance regulator (CFTR) down-regulates Na+ absorption in the colonic tissue from normal mice, our data suggest that at least some CFTR may be colocalized with the Na+ channel. Alternatively, other factors may be involved.
Grubb
B R
BR
Cystic Fibrosis/Pulmonary Research and Treatment Center, School of Medicine, The University of North Carolina at Chapel Hill, 27599, USA.
Boucher
R C
RC
D000042:Absorption; D000450:Aldosterone / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D003550:Cystic Fibrosis / Q000378:metabolism* / Q000503:physiopathology; D004594:Electrophysiology; D005260:Female; D007260:Infusion Pumps; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D051379:Mice; D012016:Reference Values; D012964:Sodium / Q000378:metabolism*
D001464:Barium; D000450:Aldosterone; D000584:Amiloride; D012964:Sodium