Wingard C J, Murphy R A
Department of Molecular Physiology and Biological Physics, University of Virginia Health Science Center, Charlottesville 22906-0011, USA.
Gen Pharmacol. 1999 Apr;32(4):483-94. doi: 10.1016/s0306-3623(98)00289-4.
Experiments were designed to examine the efficacy of the MLCK inhibitors wortmannin and ML-9 in intact smooth muscle to determine whether contractile agonists can induce a Ca(2+) and myosin light chain phosphorylation-independent contraction. Both wortmannin and ML-9 reduced active stress in a dose-dependent manner. Both inhibitors interfered with Ca2+ mobilization in either the K(+)-depolarized or agonist activated swine carotid media at concentrations greater than 10 microM. Wortmannin reduced MRLC phosphorylation and stress to resting levels in stimulated tissues while Ca2+ remained above resting levels. There was no evidence for Ca2+ and MRLC phosphorylation-independent stress generation in swine arterial smooth muscle.
设计实验以检测MLCK抑制剂渥曼青霉素和ML-9在完整平滑肌中的功效，从而确定收缩激动剂是否能诱导一种不依赖于Ca(2+)和肌球蛋白轻链磷酸化的收缩。渥曼青霉素和ML-9均以剂量依赖方式降低主动张力。两种抑制剂在浓度大于10 microM时，均可干扰K(+)去极化或激动剂激活的猪颈动脉中层的Ca2+动员。渥曼青霉素可将受刺激组织中的MRLC磷酸化和张力降低至静息水平，而Ca2+仍高于静息水平。在猪动脉平滑肌中，没有证据表明存在不依赖于Ca2+和MRLC磷酸化的张力产生。
