Studies of the cellular mechanisms underlying the vasorelaxant effects of rutaecarpine, a bioactive component extracted from an herbal drug
Studies of the cellular mechanisms underlying the vasorelaxant effects of rutaecarpine, a bioactive component extracted from an herbal drug
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DOI：
10.1097/00005344-199704000-00010
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发表时间：
1997-04-01
影响因子：
3
通讯作者：
Chen, CF
中科院分区：
文献类型：
--
作者：
Chiou, WF;Shum, AYC;Chen, CF
我们进行了从中草药吴茱萸中分离的生物碱吴茱萸次碱(RUT)的血管作用的性质和潜在机制的研究。通过大量使用苯肾上腺素(PE)对大鼠离体主动脉收缩的影响作为实验指标，并与几种已知的血管肌肉松弛药如乙酰胆碱(ACh)、组胺和A23187进行比较，RUT以浓度-(10(-7)-10(-4)M)和内皮依赖的方式松弛PE预收缩的主动脉。对合适的拮抗剂的研究表明，这与一氧化氮(NO)和鸟苷酸环化酶偶联。胞外Ca~(2+)的清除和胞内Ca~(2+)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)的处理表明，胞外Ca~(2+)内流是RUT作用的主要因素。百日咳毒素可抑制组胺的松弛作用，但不影响RUT的作用。G蛋白激活剂NaF可减弱ACh的作用，但对Na-NP、A23187和RUT的影响很小。磷脂酶C抑制剂1-[6-([17-β-3-甲氧基-1，2，3(10)-三烯-17-基]氨基}己基]-1H-吡咯-2，5-二酮(U73122)可再次抑制ACh的作用，但对A23187和RUT的作用不明显。综上所述，这些血管松弛药具有不同的细胞机制，百日咳毒素敏感的G(I)蛋白、其他G蛋白和磷脂酶C的激活都不参与吴茱萸次碱的细胞反应。
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 G(i) protein, other G proteins, nor phospholipase C activation was involved in the cellular response to rutaecarpine.