Possible Involvement of a Small G-Protein Sensitive to Exoenzyme C3 of Clostridium botulinum in the Regulation of Myofilament Ca2+ Sensitivity in β-Escin Skinned Smooth Muscle of Guinea Pig Ileum

[摘要] References(26)Cited-By(21)The effects of exoenzyme C3 of Clostridium botulinum on Ca2+ -and drug-induced tension developments were investigated in β-escin skinned smooth muscle of guinea pig ileum to test the involvement of a small G-protein in the regulation of myofilament Ca2+ sensitivity. C3 is known to ADP-ribosylate the rho p21 family of small G-proteins. Treatment with C3 (0.35 μg/ml, for 30 min) shifted the pCa-tension curve rightward along the Ca2+ concentration axis, indicating a decrease in Ca2+ sensitivity of the contractile elements. The inhibitory effect of C3 was not preserved after treatment with GDPβS (1 mM), an antagonist of GTP for the binding to G-proteins. Stimulation of muscarinic receptors with carbachol (CCh, 100 μM) shifted the pCa-tension curve leftward, indicating Ca2+ sensitization of tension development. The Ca2--sensitizing effect of CCh was not observed after C3 treatment. When GTPγS (10 μM), an activator of G-proteins, was applied at a plateau of tension development produced by a moderate concentration of Ca2+, further increase in tension was elicited and the effect of GTPγS was inhibited by C3 treatment. The results suggest the possible involvement of a rho p21-like small G-protein in the regulation of Ca2+ sensitivity of smooth muscle myofilaments.

[学科分类] 药理学

[关键词] Carbachol;Ca2+-sensitization;Smooth muscle;GTP-binding proteinn;Contraction