Hu C M, Cheng H W, Cheng Y W, Kan J J
Institute of Pharmaceutical Sciences, Taipei Medical University, Taiwan.
Jpn J Pharmacol. 2001 Jan;85(1):47-53. doi: 10.1254/jjp.85.47.
In the present study, the effect of sanguinarine (SANG) on smooth muscle was investigated in thoracic aorta isolated from rats. SANG dose-dependently relaxed the phenylephrine (PE, 3 microM)-precontracted aorta; and the concentrations to produce 50% relaxation were 3.18 +/- 0.37 and 3.42 +/- 1.14 microM, respectively, in intact and denuded aorta. These results suggest that the relaxing effect of SANG was endothelium-independent. The total contraction induced by PE was inhibited in aorta pretreated with SANG at microM concentration. Both phasic and tonic contractions induced by PE were inhibited by SANG independently, which were further supported by the fact that inositol 1,4,5-trisphosphate (IP3) formation and 45Ca2+ influx induced by 3 microM PE in denuded aorta were inhibited by SANG concentration-dependently. In addition, the vasocontraction induced by high-K+ was also inhibited by SANG, however, at higher concentrations. The inhibitory effects of SANG were reversed by dithiothreitol, a thiol reducing agent, implying that the oxidation of critical sulfhydryl groups on key molecules that regulate the smooth muscle contraction were involved. These data suggested that the inhibitory effects of SANG on PE-induced vasocontraction might involve the inhibition of IP3 formation and blockade of calcium channel.
在本研究中，研究了血根碱（SANG）对从大鼠分离的胸主动脉平滑肌的作用。SANG剂量依赖性地舒张苯肾上腺素（PE，3 microM）预收缩的主动脉；在完整和去内皮的主动脉中，产生50%舒张的浓度分别为3.18±0.37 microM和3.42±1.14 microM。这些结果表明SANG的舒张作用不依赖于内皮。在 microM浓度下用SANG预处理的主动脉中，PE诱导的总收缩受到抑制。SANG分别抑制了PE诱导的相性收缩和张力性收缩，这进一步得到以下事实的支持：在去内皮的主动脉中，3 microM PE诱导的肌醇1,4,5-三磷酸（IP3）形成和45Ca2+内流受到SANG浓度依赖性抑制。此外，高钾诱导的血管收缩也受到SANG的抑制，然而，需要更高的浓度。SANG的抑制作用被硫醇还原剂二硫苏糖醇逆转，这意味着参与调节平滑肌收缩的关键分子上的关键巯基发生了氧化。这些数据表明，SANG对PE诱导的血管收缩的抑制作用可能涉及抑制IP3形成和阻断钙通道。
