Effect of Trimebutine on Contractile Responses in Skinned Ileal Smooth Muscle.

Abstract

The effects of trimebutine on Ca 2+ release and modulation of Ca 21 sensitivity of contractile elements induced by carbachol (CCh) were investigated using a tension measuring method in p-escin-treated skinned smooth muscle of the longitudinal muscle layer of guinea pig ileum. Trimebutine (10-100 1tM) con centration-dependently inhibited tension development brought about by Ca 2+ release from intracellular stores induced by CCh (10 1M), but did not affect those induced by inositol 1,4,5-trisphosphate (IP3, 25 tiM) or caffeine (5 mM). The inhibitory effect was reversible. Trimebutine (100 pM) neither altered the Ca 21 sensitivity of the contractile elements nor affected the effects of GTPrS (50 pM) and CCh (100 pM) in poten tiating Ca 21 sensitivity of the contractile elements after the Ca 21 storage function had been eliminated by A23187. These results suggest that trimebutine inhibits CCh-induced Ca 2+ 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.

Effects of trimebutine maleate on colonic motility through Ca2+-activated K+ channels and L-type Ca2+ channels

“…Calcium antagonists or exhausted extracellular Ca 2+ blocked the increased in intracellular Ca 2+ . TM inhibited the carbachol-induced release of Ca 2+ stores in a dose-dependent manner, but did not influence the two mechanisms of Ca 2+ release (Nagasaki et al, 1994). TM inhibited the amplitude and frequency of spontaneous contractions at high concentrations, which could be ascribed to the reduction of Ca 2+ influx and release of Ca 2+ stores.…”