New therapeutic targets in ulcerative colitis: the importance of ion transporters in the human colon.
BACKGROUND
The absorption of water and ions (especially Na(+) and Cl(-)) is an important function of colonic epithelial cells in both physiological and pathophysiological conditions. Despite the comprehensive animal studies, there are only scarce available data on the ion transporter activities of the normal and inflamed human colon.


METHODS
In this study, 128 healthy controls and 69 patients suffering from ulcerative colitis (UC) were involved. We investigated the expressional and functional characteristics of the Na(+)/H(+) exchangers (NHE) 1-3, the epithelial sodium channel (ENaC), and the SLC26A3 Cl(-)/HCO 3- exchanger downregulated in adenoma (DRA) in primary colonic crypts isolated from human biopsy and surgical samples using microfluorometry, patch clamp, and real-time reverse-transcription polymerase chain reaction (RT-PCR) techniques.


RESULTS
Data collected from colonic crypts showed that the activities of electroneutral (via NHE3) and the electrogenic Na(+) absorption (via ENaC) are in inverse ratio to each other in the proximal and distal colon. We found no significant differences in the activity of NHE2 in different segments of the colon. Surface cell Cl(-)/HCO 3- exchange is more active in the distal part of the colon. Importantly, both sodium and chloride absorptions are damaged in UC, whereas NHE1, which has been shown to promote immune response, is upregulated by 6-fold.


CONCLUSIONS
These results open up new therapeutic targets in UC.
Farkas
Klaudia
K
First Department of Medicine, University of Szeged, Szeged, Hungary.
Yeruva
Sunil
S
Rakonczay
Zoltán
Z
Ludolph
Lisa
L
Molnár
Tamás
T
Nagy
Ferenc
F
Szepes
Zoltán
Z
Schnúr
Andrea
A
Wittmann
Tibor
T
Hubricht
Jessica
J
Riederer
Brigitte
B
Venglovecz
Viktória
V
Lázár
György
G
Király
Marianna
M
Zsembery
Ákos
Á
Varga
Gábor
G
Seidler
Ursula
U
Hegyi
Péter
P
D017920:Antiporters / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D027963:Chloride-Bicarbonate Antiporters; D002712:Chlorides / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000235:genetics / Q000378:metabolism* / Q000601:surgery; D003106:Colon / Q000378:metabolism*; D053503:Epithelial Sodium Channels / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017136:Ion Transport; D012964:Sodium / Q000378:metabolism; D000074082:Sodium-Hydrogen Exchanger 1; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics / Q000378:metabolism*; D000076988:Sulfate Transporters
D017920:Antiporters; D027682:Cation Transport Proteins; D027963:Chloride-Bicarbonate Antiporters; D002712:Chlorides; D053503:Epithelial Sodium Channels; C081011:SLC26A3 protein, human; C490998:SLC9A1 protein, human; C081517:SLC9A2 protein, human; C000613385:SLC9A3 protein, human; D000074082:Sodium-Hydrogen Exchanger 1; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D000076988:Sulfate Transporters; D012964:Sodium