Altered contractility of circular and longitudinal muscle in TNBS-inflamed guinea pig ileum.
Intestinal motility disorders are often associated with gut inflammation. We evaluated, in vitro under isometric conditions, changes in contractility of longitudinal and circular muscle layers from guinea pig ileum 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, contractile responses to receptor agonists were differentially altered in both layers in comparison with controls. Thus, in longitudinal strips from TNBS-treated ileum, there was a twofold increase in maximal response (Emax) induced by carbachol and histamine without modification of 50% effective concentration (EC50) values; responses to 5-hydroxytryptamine (5-HT) were not modified; both alpha 1- and alpha 2-adrenoceptor-mediated responses to epinephrine were abolished. In circular strips, inflammation did not affect the Emax induced by carbachol and histamine but led to increased EC50 values; Emax to 5-HT was reduced without 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 inflamed circular strips. The results indicate that in the guinea pig model of TNBS-induced ileitis, the in vitro contractile responses of circular and longitudinal smooth muscle to the stimulation of various receptors are differentially altered, whereas non-receptor-mediated contraction to KCl depolarization is not modified.
Martinolle
J P
JP
Institut National de la Recherche Agronomique, Pharmacology and Toxicology Unit, Toulouse, France.
Garcia-Villar
R
R
Fioramonti
J
J
Bueno
L
L
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002908:Chronic Disease; D004751:Enteritis / Q000503:physiopathology*; D004837:Epinephrine / Q000494:pharmacology; D005769:Gastrointestinal Motility / Q000187:drug effects; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000503:physiopathology*; D010277:Parasympathomimetics / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D013997:Time Factors; D014302:Trinitrobenzenesulfonic Acid
D000316:Adrenergic alpha-Agonists; D010277:Parasympathomimetics; D012701:Serotonin; D011189:Potassium Chloride; D014302:Trinitrobenzenesulfonic Acid; D002217:Carbachol; D004837:Epinephrine