Intestinal barrier function in health and disease

The intestinal epithelium has the dual function of absorbing nutrients and water as well as being a barrier to potentially harmful substances such as macromolecules and bacteria. In the present thesis the barrier function of the intestinal mucosa was studied in vitro in Ussing diffusion chambers. Intestinal permeability to different-sized molecules was investigated and compared in various intestinal regions and species. A size-dependent permeability was found; the smaller the molecules the greater the permeability. In man and pig a higher permeation to small and medium-sized markers was found in the proximal part of the intestine compared to the distal part. The rat deviated with a higher permeability in the distal small intestine. No differences in permeability were observed for macromolecules. Intestinal mucosa from patients with ulcerative colitis, patients subjected to radiation therapy and colonic mucosa used for reconstruction of the urinary tract were compared with apparently normal colonic mucosa obtained from patients undergoing surgical resection due to cancer in the intestinal tract. Colonic mucosa from patients with ulcerative colitis and irradiated rectal mucosa showed an increased permeation of different-sized marker molecules. The permeability in the colonic mucosa in chronic contact with urine from patients with urine reservoirs was, however, unaltered. A decreased permeability in both ileal and colonic transplanted mucosa was demonstrated in a rat enterocystoplasty model. The effect of pituitary adenylate cyclase activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) on epithelial ion transport in human sigmoid colon was investigated using the short-circuit current (Isc) as an index of ion transport. PACAP-27, PACAP-38 and VIP all produced concentration-dependent (10-10-10-6 M) increases in Isc. Tetrodotoxin almost completely blocked the PACAP-38-evoked Isc response whereas it shifted the PACAP-27 curve to the right and had no effect on VIP. Atropine did not inhibit the PACAP-or the VIP-evoked responses, suggesting a non-muscarinic mechanism of action. The results suggest that PACAP exerts its action on enteric neurons whereas VIP acts on the epithelial cells.