EFFECT OF TRIMEBUTINE ON CONTRACTILE RESPONSES IN SKINNED ILEAL SMOOTH-MUSCLE

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 beta-escin-treated skinned smooth muscle of the longitudinal muscle layer of guinea pig ileum. Trimebutine (10-100 mu M) concentration-dependently inhibited tension development brought about by Ca2+ release from intracellular stores induced by CCh (1O mu M), but did not affect those induced by inositol 1,4,5-trisphosphate (IP3, 25 mu M) or caffeine (5 mM). The inhibitory effect was reversible. Trimebutine(100 mu M) neither altered the Ca2+ sensitivity of the contractile elements nor affected the effects of GTP gamma S (50 mu M) and CCh (100 mu 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.