Chiou W F, Shum A Y, Liao J F, Chen C F
National Research Institute of Chinese Medicine, National Yang-Ming University, Taipei, Taiwan, R.O.C.
J Cardiovasc Pharmacol. 1997 Apr;29(4):490-8. doi: 10.1097/00005344-199704000-00010.
We conducted studies to investigate the nature and underlying mechanisms of the vascular effects of rutaecarpine (Rut), an alkaloid isolated from the Chinese herbal drug Evodia rutaecarpa. By using largely the effects on phenylephrine (PE)-induced contraction in the isolated rat aorta as the experimental index and by comparison with several known vascular muscle relaxants such as acetylcholine (ACh), histamine, and A23187, Rut relaxed PE-precontracted aorta in concentration-(10(-7)-10(-4) M) and endothelium-dependent manners. Studies with appropriate antagonists indicated that this was coupled to nitric oxide (NO) and guanylyl cyclase. Extracellular Ca2+ removal and treatment with the intracellular Ca2+ antagonist, 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8), suggested that influx of extracellular Ca2+ was the major factor contributing to the action of Rut. Pertussis toxin suppressed the relaxation potency of histamine but had no effects on the actions of Rut. NaF, the G proteins activator, attenuated the actions of ACh, but only minimally affected Na-NP, A23187, and Rut. 1-[6-{[17 beta-3-methoxyestra-1,2,3(10)-trien-17-yl]amino} hexyl]-1H-pyrrole-2,5-dione (U73122), the phospholipase C inhibitor, again suppressed the actions of ACh but had few effects on A23187 and Rut. Taken together, these results suggest that these vasorelaxants had different cellular mechanisms and that neither pertussis toxin-sensitive Gi protein, other G proteins, nor phospholipase C activation was involved in the cellular response to rutaecarpine.
我们开展了多项研究，以探究吴茱萸碱（Rut）——一种从中药材吴茱萸中分离得到的生物碱——对血管作用的性质及潜在机制。主要以其对去氧肾上腺素（PE）诱导的离体大鼠主动脉收缩的影响作为实验指标，并与几种已知的血管平滑肌舒张剂如乙酰胆碱（ACh）、组胺和A23187进行比较，结果显示，Rut能以浓度依赖（10⁻⁷ - 10⁻⁴ M）且依赖内皮的方式舒张PE预收缩的主动脉。使用合适拮抗剂的研究表明，这与一氧化氮（NO）和鸟苷酸环化酶有关。细胞外Ca²⁺去除以及用细胞内Ca²⁺拮抗剂8 - （N，N - 二乙氨基）辛基 - 3，4，5 - 三甲氧基苯甲酸酯（TMB - 8）处理表明，细胞外Ca²⁺内流是Rut发挥作用的主要因素。百日咳毒素抑制组胺的舒张效能，但对Rut的作用无影响。G蛋白激活剂氟化钠（NaF）减弱ACh的作用，但仅对硝普钠（Na - NP）、A23187和Rut有轻微影响。磷脂酶C抑制剂1 - [6 - {[17β - 3 - 甲氧基雌甾 - 1，2，3（10） - 三烯 - 17 - 基]氨基}己基] - 1H - 吡咯 - 2，5 - 二酮（U73122）同样抑制ACh的作用，但对A23187和Rut影响较小。综上所述，这些结果表明这些血管舒张剂具有不同的细胞机制，并且百日咳毒素敏感的Gi蛋白、其他G蛋白以及磷脂酶C激活均不参与细胞对吴茱萸碱的反应。
