Chloride conductance and sodium-dependent glucose transport in rat and human enterocytes.
OBJECTIVE
In cystic fibrosis intestine, there is an increase in the rate of Na+-dependent glucose absorption. This may result from enterocyte hyperpolarization after defective Cl- channel function, but only if Cl- secretion and Na+/glucose cotransport occur in the same membrane. This study examined the effects of Cl- gradients on Na+/glucose uptake in brush border membrane vesicles from rat and human small intestine.


METHODS
Vesicles were prepared by Mg2+-precipitation, and the active uptake of tritiated glucose was measured using a filtration-stop protocol.


RESULTS
An outwardly directed Cl- gradient inhibited active glucose uptake in rat vesicles, whereas an inward Cl- gradient stimulated uptake. These effects were sensitive to blockers of the cystic fibrosis transmembrane regulator but not to inhibitors of other Cl- channels. Active glucose uptake into vesicles prepared from normal human intestine was also inhibited by an outward Cl- gradient, whereas uptake into vesicles prepared from a single sample of human cystic fibrosis intestine was not.


CONCLUSIONS
A Cl- conductance resembling the cystic fibrosis transmembrane regulator is colocalized with Na+/glucose cotransport in rat and human small intestine, supporting the possibility that abnormalities in glucose absorption in cystic fibrosis may be a secondary effect of defects in Cl- channel function.
Beesley
A H
AH
Department of Biomedical Science, Sheffield University, England.
Hardcastle
J
J
Hardcastle
P T
PT
Taylor
C J
CJ
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000818:Animals; D018118:Chloride Channels / Q000037:antagonists & inhibitors; D002712:Chlorides / Q000378:metabolism*; D005947:Glucose / Q000493:pharmacokinetics; D006801:Humans; D007421:Intestine, Small / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008871:Microvilli / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009579:Nitrobenzoates / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D051269:Sodium-Glucose Transporter 1; D062367:ortho-Aminobenzoates / Q000494:pharmacology
D018118:Chloride Channels; D002712:Chlorides; D008562:Membrane Glycoproteins; D009004:Monosaccharide Transport Proteins; D009579:Nitrobenzoates; C495674:SLC5A1 protein, human; C495676:Slc5a1 protein, rat; D051269:Sodium-Glucose Transporter 1; D062367:ortho-Aminobenzoates; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; C001209:fenamic acid; D005947:Glucose; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid