Effect of Trimebutine on Contractile Responses in Skinned Ileal Smooth Muscle

[摘要] References(24)Cited-By(3)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.

[学科分类] 药理学

[关键词] Trimebutine;Skinned smooth muscle;Muscle contraction;Calcium storage;Calcium sensitivity