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 microM) concentration-dependently inhibited tension development brought about by Ca2+ release from intracellular stores induced by CCh (10 microM), but did not affect those induced by inositol 1,4,5-trisphosphate (IP3, 25 microM) or caffeine (5 mM). The inhibitory effect was reversible. Trimebutine (100 microM) neither altered the Ca2+ sensitivity of the contractile elements nor affected the effects of GTP gamma S (50 microM) and CCh (100 microM) 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.
Nagasaki
M
M
Pharmacological Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan.
Itagaki
M
M
Komori
S
S
Ohashi
H
H
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004594:Electrophysiology; D004928:Escin / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism; D014287:Trimebutine / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000378:metabolism
D011976:Receptors, Muscarinic; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D000001:Calcimycin; D002110:Caffeine; D004928:Escin; D015544:Inositol 1,4,5-Trisphosphate; D002217:Carbachol; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D014287:Trimebutine; D002118:Calcium