Itagaki M, Komori S, Unno T, Syuto B, Ohashi H
Department of Veterinary Science, Faculty of Agriculture, Gifu University, Japan.
Jpn J Pharmacol. 1995 Jan;67(1):1-7. doi: 10.1254/jjp.67.1.
The effects of exoenzyme C3 of Clostridium botulinum on Ca(2+)- and drug-induced tension developments were investigated in beta-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 microgram/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 GDP beta S (1 mM), an antagonist of GTP for the binding to G-proteins. Stimulation of muscarinic receptors with carbachol (CCh, 100 microM) shifted the pCa-tension curve leftward, indicating Ca2+ sensitization of tension development. The Ca(2+)-sensitizing effect of CCh was not observed after C3 treatment. When GTP gamma S (10 microM), 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 GTP gamma S 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.
研究了肉毒杆菌外切酶C3对豚鼠回肠β-七叶皂苷去表皮平滑肌中钙和药物诱导的张力发展的影响，以测试小G蛋白在调节肌丝钙敏感性中的作用。已知C3可使小G蛋白的rho p21家族进行ADP核糖基化。用C3（0.35微克/毫升，处理30分钟）处理后，pCa-张力曲线沿钙浓度轴向右移动，表明收缩元件的钙敏感性降低。在用GDPβS（1毫摩尔）处理后，C3的抑制作用消失，GDPβS是一种GTP与G蛋白结合的拮抗剂。用卡巴胆碱（CCh，100微摩尔）刺激毒蕈碱受体可使pCa-张力曲线向左移动，表明张力发展的钙敏化。C3处理后未观察到CCh的钙敏化作用。当在中等浓度钙产生的张力发展平台期应用G蛋白激活剂GTPγS（10微摩尔）时，可引起张力进一步增加，且GTPγS的作用被C3处理所抑制。结果表明，rho p21样小G蛋白可能参与平滑肌肌丝钙敏感性的调节。
