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Mediators of Inflammation
Volume 12, Issue 1, Pages 21-27
http://dx.doi.org/10.1080/0962935031000096944

Effect of pharmacologically induced smooth muscle activation on permeability in murine colitis

1Department of Anesthesiology, Erasmus Medical Centre, P.O. Box. 2040, Rotterdam 3000 CA, The Netherlands
2Numico Research, Wageningen, The Netherlands
3Department of Pharmacology, Erasmus Medical Centre, The Netherlands
4Department of Gastroenterology, Medical Centre Haaglanden, The Netherlands

Copyright © 2003 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background: Both intestinal permeability and contractility are altered in inflammatory bowel disease. Little is known about their mutual relation. Therefore, an in vitro organ bath technique was developed to investigate the simultaneous effects of inflammation on permeability and smooth muscle contractility in different segments of the colon.

Methods and materials: BALB/c mice were exposed to a 10% dextran sulphate sodium drinking water solution for 7 days to induce a mild colitis, while control mice received normal tap water. Intestinal segments were placed in an oxygenated organ bath containing Krebs buffer. Permeability was measured by the transport of the marker molecules 3H-mannitol and 14C-polyethyleneglycol 4000. Contractility was measured through a pressure sensor. Smooth muscle relaxation was obtained by salbutamol and l-phenylephrine, whereas contraction was achieved by carbachol and 1-(3-chlorophenyl)-biguanide.

Results: The intensity of mucosal inflammation increased throughout the colon. Also, regional differences were observed in intestinal permeability. In both normal and inflamed distal colon segments, permeability was diminished compared with proximal colon segments and the non-inflamed ileum. Permeability in inflamed distal colon segments was significantly decreased compared with normal distal segments. Pharmacologically induced relaxation of smooth muscles did not affect this diminished permeability, although an increased motility positively affected permeability in inflamed and non-inflamed distal colon.

Conclusions: Inflammation and permeability is inversely related. The use of pro-kinetics could counteract this disturbed permeability and, in turn, could regulate the disturbed production of inflammatory mediators.