Aims: 

This study evaluated the time course of disturbances of colonic chloride secretion during experimental colitis.

Methods: 

Colitis was induced by treatment of Balb/c mice with 2% dextran sodium sulphate (DSS) in drinking water for 5 days. At different time points during or after induction of colitis the effect of secretagogues, histamine (5.10^-4 M), carbachol (10^-4 M) and 5-hydroxytryptamine (10^-4 M), was studied under short-circuit conditions in the absence or presence of tetrodotoxin (10^-6 M). In addition, histological scores were evaluated and transcript levels of some inflammatory markers were measured using real-time quantitative RT-PCR.

Results: 

Whereas, the markers of inflammation were elevated, the TTX-sensitive (ENS mediated) pro-secretory tonus has not been increased. In inflamed tissue the cholinergic agonist carbachol was either without any effect on chloride secretion or even decreases it (-5.0 ± 3.0 mA.cm^-2, resp. -5.6 ± 4.0 mA.cm^-2, vs. 25 ± 3.6 mA.cm^-2 in control). In healthy animals, the stimulatory effect of carbachol was higher in the absence of TTX (25 ± 3.6 mA.cm^-2 vs. 10.8 ± 0.6 mA.cm^-2). In contrast, DSS-treated mice showed higher responsiveness to carbachol in the presence of TTX but only during the first two days, especially the second day (36.0 ± 8.9 mA.cm^-2 vs. 20.2 ± 3.1 mA.cm^-2). The effect of 5-HT was higher in the presence of TTX in mice exposed to DSS within the first four days, but 2 and 4 weeks later the response to 5-HT was independent of TTX similar to control animals.

Conclusion: 

This data suggests changes of the gut nervous system in the early phase of experimental colitis.

Supported by grant 305/ 07/ 0328 from GACR.