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Am J Physiol Gastrointest Liver Physiol 277: G61-G68, 1999;
0193-1857/99 $5.00
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Vol. 277, Issue 1, G61-G68, July 1999

Differential changes in ACh-, motilin-, substance P-, and K+-induced contractility in rabbit colitis

Inge Depoortere1, Gert van Assche1, Theo Thijs1, Karel Geboes2, and Theo L. Peeters1

1 Gut Hormone Laboratory, Department of Pathophysiology, and 2 Department of Morphology and Imaging, Katholieke Universiteit Leuven, Louvain B-3000, Belgium

To test the hypothesis that the changes in intestinal contractility, which accompany inflammation of the gut, are agonist specific, we compared the response of inflamed strips to substance P (SP), motilin, ACh, and K+ as a function of time. In parallel experiments, changes in the general mechanical properties (passive tension, optimal stretch) of the colitic tissue were evaluated. Colitis was induced by trinitrobenzenesulfonic acid, and rabbits were killed after 1, 2, 3, 5, or 8 days. Passive tension was increased starting from day 2 until day 8, and maximal active tension (Tmax) was generated at less stretch from day 5. A 50% decrease in Tmax was observed for ACh and K+ between days 2 and 3 and for motilin and SP between days 3 and 5. For all compounds, Tmax returned to normal after 8 days. The pEC50 value (negative logarithm of the concentration that induces 50% of the maximal contractile activity) for ACh was increased from day 3 until day 8 and for SP at day 3, whereas for motilin it was decreased at day 1. The changes in passive tension and optimal stretch indicate generalized structural alterations of smooth muscle tissue. However, the different time profiles of the changes in active tension and contractile potency for different contractile agents suggest that inflammation specifically affects receptor-mediated mechanisms.

inflammation; 2,4,6-trinitrobenzenesulfonic acid; in vitro smooth muscle contraction; length-tension


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