Effect of pharmacologically induced smooth muscle activation on permeability in murine colitis.
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
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.
Zijlstra
Freek J
FJ
Department of Anesthesiology, Erasmus Medical Centre, PO Box 2040, 3000 CA Rotterdam, the Netherlands. zijlstra@anes.azr.nl
van Meeteren
Marieke E
ME
Garrelds
Ingrid M
IM
Meijssen
Maarten A C
MA
D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D001645:Biguanides / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D003092:Colitis / Q000139:chemically induced / Q000503:physiopathology*; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D005260:Female; D007408:Intestinal Absorption / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D009924:Organ Culture Techniques / Q000379:methods; D010539:Permeability; D010656:Phenylephrine / Q000494:pharmacology
D001645:Biguanides; D010656:Phenylephrine; D002217:Carbachol; D016264:Dextran Sulfate; C065734:1-(3-chlorophenyl)biguanide; D000420:Albuterol