Z Gastroenterol 2009; 47 - A18
DOI: 10.1055/s-0029-1223997

Investigation of ion transport activities in normal and ulcerative colitis human colonic epithelial cells

K Farkas 1, S Yeruva 2, J Hubricht 2, Z Rakonczay Jr 1, F Nagy 1, T Molnár 1, Z Szepes 1, L Varga 3, V Venglovecz 4, T Wittmann 1, B Riederer 2, U Seidler 2, P Hegyi 1
  • 1First Department of Medicine, University of Szeged, Szeged
  • 2Department of Gastroenterology, Hannover Medical School, Hannover
  • 3Department of Surgery, University of Szeged, Szeged
  • 4Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged

Introduction: It has been shown in animal studies that acid/base transporters influence the activities of inflammatory process in inflammatory bowel diseases. There are only scarce available data on the activities of these ion transporters in the normal and inflamed human colon.

The aims of our study were to determine the resting intracellular pH (pHi), the activities of Na+/H+ exchangers (NHEs) and the Cl-/HCO3- exchangers (AEs) in colonic crypts isolated from patients with mild or moderate ulcerative colitis [UC] and patients with no colonic disease.

Methods: 6 colonic biopsies were obtained from each patient (n=48 for control, n=19 for UC) undergoing colonoscopy or colon surgery. Colonic crypts were isolated and then loaded with the pH sensitive fluorescent dye BCECF. Fluorescence intensity was detected from different parts of the crypts by an OLYMPUS Cell R imaging system. The activity of AE was measured by the Cl- removal technique, whereas the activity of NHEs was measured by the ammonium pulse technique. mRNA expression of NHE1, 3, and the NHE3 regulatory PDZ-adaptors NHERF1 and PDZK1 were measured by real-time PCR.

Results: The activity of NHE1 was significantly higher in the proximal vs. the distal part of the normal colon. No differences were observed in NHE2 activities of the different parts of the colon. The activity of NHE3 was the highest in the surface of the crypts isolated from the proximal colon and also showed a decreasing pattern from the proximal part to the distal part of the colon. The activity of NHE1 was significantly higher whereas the activities of NHE3 and AE were significantly lower in UC vs. the control crypts. The mRNA level of NHE1 was significantly upregulated, whereas PDZK1 was downregulated in UC vs. control crypts. No differences were found in the mRNA levels of NHE3 and NHERF1.

Conclusions: NHE activities are altered in the colonic crypts of UC vs. control patients. These differences in NHE activities may influence the disease activity and may also lead to impaired Na+ and water absorption.

Supported by OTKA, MTA and NKTH.