Differential inflammatory modulation of canine ileal longitudinal and circular muscle cells

Abstract

The aim of this study was to identify the subtypes of muscarinic receptors that mediate in vivo and in vitro canine ileal longitudinal muscle contractions and whether their role is modulated by inflammation. Previous studies have reported that circular muscle contractions are suppressed in ileal inflammation induced by mucosal exposure to ethanol and acetic acid. We found that inflammation had no significant effect on in vivo and in vitro spontaneous or muscarinic receptor-mediated contractions of the longitudinal muscle. The longitudinal muscle contractions were mediated primarily by the M3 receptor subtype. However, the IC50 of the M2 receptor antagonist methoctramine was only 10 times greater than that of the M3 receptor antagonist 4-DAMP in the longitudinal muscle, whereas it was 224 times greater in the circular muscle. M2receptor-coupled decrease of intracellular cAMP occurred in the longitudinal but not in the circular muscle from the normal ileum. Inflammation did not alter this coupling in the longitudinal muscle but established it in the circular muscle. In conclusion, M2 receptors may play a greater role in the mediation of longitudinal muscle contractions than circular muscle contractions. Inflammation does not alter the contractility or the relative role of muscarinic receptor subtypes in longitudinal muscle cells. However, it modulates the M2 receptor coupling to adenylate cyclase in the circular muscle.