Regional intestinal adaptations in Na+,K+-ATPase in experimental colitis and the contrasting effects of interferon-gamma.
OBJECTIVE
This study evaluated Na+,K+-ATPase activity and the abundance of alpha1 subunit Na+,K+-ATPase in experimental colitis and gathered evidence on the effects of interferon-gamma (IFN-gamma) on intestinal Na+,K+-ATPase.


METHODS
Colitis was induced by the intrarectal administration of 2,4,6-trinitrobenzene sulphonic acid (TNBS, 30 mg/250 microL). Na+,K+-ATPase activity was determined as the difference between total and ouabain-insensitive ATPase. The abundance of Na+,K+-ATPase was analysed by immunoblotting.


RESULTS
Na+,K+-ATPase activity was markedly reduced in the proximal colonic mucosa of TNBS-treated rats, whereas upstream in the terminal ileal mucosa a marked increase in sodium pump activity was observed. At the jejunal level no significant changes in Na+,K+-ATPase activity were observed between TNBS-treated rats and corresponding controls (ethanol-treated rats). No changes were observed in the abundance of alpha1 subunit Na+,K+-ATPase in the proximal colon, terminal ileum and jejunum. The administration of IFN-gamma (50,000 U) 48 h before sacrifice reduced both Na+,K+-ATPase activity and the abundance of alpha1 subunit Na+,K+-ATPase in the proximal colon. Dexamethasone prevented colonic inflammation and decreases in proximal colonic Na+,K+-ATPase activity in TNBS-treated rats, but did not affect the INF-gamma-induced decrease in colonic Na+,K+-ATPase activity.


CONCLUSIONS
The increase in ileal Na+,K+-ATPase activity upstream to the lesioned colonic mucosa, where Na+,K+-ATPase activity was markedly reduced, might indicate a compensatory process to counteract the decrease in water and electrolyte absorption at the colonic level. This decrease in colonic Na+,K+-ATPase activity is likely not related to INF-gamma-induced downregulation of Na+,K+-ATPase.
Magro
F
F
Institute of Pharmacology and Therapeutics, Faculty of Medicine, Porto, Portugal.
Fraga
S
S
Ribeiro
T
T
Soares-da-Silva
P
P
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D018938:Caco-2 Cells / Q000187:drug effects; D003092:Colitis / Q000378:metabolism*; D003106:Colon / Q000187:drug effects / Q000201:enzymology; D003907:Dexamethasone / Q000494:pharmacology; D004847:Epithelial Cells / Q000201:enzymology; D006801:Humans; D007082:Ileum / Q000187:drug effects / Q000201:enzymology; D007371:Interferon-gamma / Q000097:blood / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000201:enzymology; D007583:Jejunum / Q000187:drug effects / Q000201:enzymology; D041741:Lower Gastrointestinal Tract / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D000970:Antineoplastic Agents; D003907:Dexamethasone; D007371:Interferon-gamma; D009195:Peroxidase; D000254:Sodium-Potassium-Exchanging ATPase