ALTERED CONTRACTILITY OF CIRCULAR AND LONGITUDINAL MUSCLE IN TNBS-INFLAMED GUINEA-PIG ILEUM

Intestinal motility disorders are often associated with gut inflammati on. We evaluated, in vitro under isometric conditions, changes in cont ractility of longitudinal and circular muscle layers from guinea pig i leum after 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced ileitis. TNBS treatment did not modify length-active tension relationships for both muscle layers, whereas a significant increase in passive tension was observed in the circular muscle response to stretching. Moreover, in both control and inflamed strips at optimal stretch, concentration- response curves to KCl were similar for both layers. In contrast, cont ractile responses to receptor agonists were differentially altered in both layers in comparison with controls. Thus, in longitudinal strips fi om TNBS-treated ileum, there was a twofold increase in maximal resp onse (E-max) induced by carbachol and histamine without modification o f 50% effective concentration (EC50) values; responses to 5-hydroxytry ptamine (5-HT) were not modified; both alpha(1)- and alpha(2)-adrenoce ptor-mediated responses to epinephrine were abolished. In circular str ips, inflammation did not affect the E-max induced by carbachol and hi stamine but led to increased EC50 values; E-max to 5-HT was reduced wi thout change in EC50 values. Moreover, in the dose range used (0.1 nM to 0.1 mM), a maximal response to carbachol was not obtained in inflam ed circular strips. The results indicate that in the guinea pig model of TNBS-induced ileitis, the in vitro contractile responses of circula r and longitudinal smooth muscle to the stimulation of various recepto rs are differentially altered, whereas non-receptor-mediated contracti on to KCl depolarization is not modified.