Ion transport across the normal and CF neonatal murine intestine.
Neonatal mice with cystic fibrosis (CF) exhibit a very high mortality due to intestinal obstruction localized primarily to the ileum and colon. It has been hypothesized that lack of Cl(-) secretion and possibly elevated Na(+) absorption contribute to the gut problems in CF neonates. Therefore, intestines (ileum, proximal colon, and distal colon) from normal and CF day-old mouse pups were studied on ultra-small-aperture (0.0135 cm(2)) Ussing chambers. All three regions of the normal neonatal intestine responded to forskolin with an increase in short-circuit current, which was completely absent in the CF intestine. The neonatal distal colon exhibited a high rate of amiloride-sensitive electrogenic Na(+) absorption, which did not differ between the normal and CF preparations. The ileum and proximal colon of both genotypes exhibited a small but significant electrogenic Na(+) absorption. The neonatal proximal colon and ileum also exhibited electrogenic Na(+)-glucose cotransport, which was significantly greater in the normal compared with the CF ileum. In addition, all three intestinal regions exhibited electrogenic Na(+)-alanine cotransport, which was significantly reduced in two of the regions of the CF neonatal intestine. It is speculated that: 1) the reduced rate of Na(+)-nutrient cotransport in the CF intestine contributes to the lower rate of growth in CF pups, whereas 2) the elevated electrogenic Na(+) absorption in the neonatal intestine, coupled with an inability to secrete Cl(-), contributes to the intestinal obstruction in the CF pups.
Grubb
B R
BR
Cystic Fibrosis/Pulmonary Research and Treatment Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7248, USA. bgrubb@med.unc.edu
D000584:Amiloride / Q000494:pharmacology; D026905:Amino Acid Transport Systems; D026921:Amino Acid Transport Systems, Neutral; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D003550:Cystic Fibrosis / Q000378:metabolism*; D004563:Electrochemistry; D004594:Electrophysiology; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects / Q000502:physiology; D017136:Ion Transport / Q000502:physiology; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D012016:Reference Values; D012964:Sodium / Q000378:metabolism; D051269:Sodium-Glucose Transporter 1; D027981:Symporters
D026905:Amino Acid Transport Systems; D026921:Amino Acid Transport Systems, Neutral; D002352:Carrier Proteins; D002712:Chlorides; D008562:Membrane Glycoproteins; D009004:Monosaccharide Transport Proteins; C495675:Slc5a1 protein, mouse; D051269:Sodium-Glucose Transporter 1; D027981:Symporters; C052168:sodium-alanine cotransporter; D005576:Colforsin; D000584:Amiloride; D002217:Carbachol; D012964:Sodium