Effect of Trimebutine on Contractile Responses in Skinned Ileal Smooth Muscle

Abstract

The effects of trimebutine on Ca²⁺ release and modulation of Ca²⁺ sensitivity of contractile elements induced by carbachol (CCh) were investigated using a tension measuring method in β-escin-treated skinned smooth muscle of the longitudinal muscle layer of guinea pig ileum. Trimebutine (10-100 μM) concentration-dependently inhibited tension development brought about by Ca²⁺ release from intracellular stores induced by CCh (10 μM), but did not affect those induced by inositol 1, 4, 5-trisphosphate (IP₃, 25 μM) or caffeine (5 mM). The inhibitory effect was reversible. Trimebutine (100 μM) neither altered the Ca²⁺ sensitivity of the contractile elements nor affected the effects of GTPγS (50 ²⁺M) and CCh (100 ²⁺M) in potentiating Ca²⁺ sensitivity of the contractile elements after the Ca²⁺ storage function had been eliminated by A23187. These results suggest that trimebutine inhibits CCh-induced Ca²⁺ release by acting at some point during the coupling of muscarinic receptors through a G-protein to phospholipase C and thus reducing the accumulation of IP₃.