• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Naunyn-Schmiedeberg's Archives of Pharmacology >In vitro vasodilator mechanisms of the indole alkaloids rhynchophylline and isorhynchophylline, isolated from the hook of Uncaria rhynchophylla (Miquel)
【24h】

In vitro vasodilator mechanisms of the indole alkaloids rhynchophylline and isorhynchophylline, isolated from the hook of Uncaria rhynchophylla (Miquel)

机译：从钩藤Uncaria rhynchophylla（Miquel）的钩中分离出来的吲哚生物碱类花茶碱和异吗啉茶碱的体外血管舒张机制

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Rhynchophylline (Rhy) and isorhynchophylline (Isorhy), indole alkaloids from Uncaria hooks, reportedly exert hypotensive and vasodilatory effects, but the mechanism of action is unclear. We therefore investigated the relaxant effects of these two isomeric alkaloids in rat arteries in vitro, in particular in respect of the various functional Ca2+ pathways. Both Rhy and Isorhy relaxed aortic rings precontracted with phenylephrine (PE, 1 µM) in a dose-dependent manner (3–300 µM). Removal of endothelium and preincubation with L-NAME (300 µM) slightly inhibited but did not prevent the relaxant response. These results indicate that Rhy and Isorhy act largely in an endothelium-independent manner. Unlike nicardipine, both alkaloids not only inhibited the contraction induced by 60 mM KCl (IC50 20–30 µM), but also that induced by PE and U46619, albeit to a lesser extent (IC50 100 and 200 µM, respectively). These results suggest that Rhy and Isorhy may act via multiple Ca2+ pathways. In contrast to their inhibitory effects on KCl-induced and receptor-mediated contractions, where both isomers were comparably potent, Rhy was more potent than Isorhy at higher concentrations (>100 µM) in inhibiting both caffeine (25 mM)- and cyclopiazonic acid (CPA, 30 µM)-induced contractions. Similar results observed with caffeine in Ca2+-containing medium were also observed in Ca2+-free medium. However, 0.1–0.3 µM nicardipine (which completely inhibited KCl-induced contraction) had no significant inhibitory effect on CPA-induced contractions. Taken together, these results indicate discrimination between these two isomers with respect to Ca2+-induced Ca2+ release and non-L-type Ca2+ channel, but not for IP3-induced Ca2+ release and L-type Ca2+ channels. Similar relaxant responses to KCl- and caffeine-induced contractions were seen when these two alkaloids were tested on the smaller mesenteric and renal arteries. In conclusion, the vasodilatory effects of Rhy and Isorhy are largely endothelium independent and are mediated by L-type Ca2+ channels. At higher concentrations, they also affect other Ca2+-handling pathways, although to a lesser extent. While there is no discrimination between the two isomers with respect to the contraction induced by KCl or agonists (PE and U46619), differential effects between Rhy and Isorhy were seen on caffeine- and CPA-induced contractions.
机译：据报道，钩藤钩的吲哚生物碱-鼻支茶碱（Rhy）和异去甲茶碱（Isorhy）具有降压和血管舒张作用，但作用机理尚不清楚。因此，我们研究了这两种异构生物碱在大鼠动脉中的松弛作用，特别是在各种功能性Ca2 + 途径方面。 Rhy和Isorhy均以剂量依赖性（3–300 µM）与苯肾上腺素（PE，1 µM）预收缩了松弛的主动脉环。去除内皮细胞和用L-NAME（300 µM）预孵育会略有抑制，但不能阻止松弛反应。这些结果表明Rhy和Isorhy在很大程度上独立于内皮细胞。与尼卡地平不同，两种生物碱不仅抑制60 mM KCl（IC50 20–30 µM）诱导的收缩，而且抑制PE和U46619诱导的收缩，尽管程度较小（IC50 100和200）分别为µM）。这些结果表明，Rhy和Isorhy可能通过多种Ca2 + 途径起作用。与它们对KCl诱导的和受体介导的收缩的抑制作用相反（后者在两种异构体中均具有较强的抑制作用），在较高浓度（> 100 µM）下，Rhy比Isorhy在抑制咖啡因（25 mM）和环吡唑啉酸方面更有效（ CPA，30 µM）引起的收缩。在不含Ca2 +的培养基中，咖啡因在含Ca2 +的培养基中也观察到相似的结果。但是，0.1–0.3 µM尼卡地平（完全抑制KCl诱导的收缩）对CPA诱导的收缩没有明显的抑制作用。综上所述，这些结果表明这两种异构体在Ca 2+诱导的Ca 2+释放和非L型Ca 2+通道方面存在区别，但对于IP 3诱导的却没有区别。 Ca2 + 释放和L型Ca2 + 通道。当在较小的肠系膜和肾动脉上测试这两种生物碱时，可以看到对KCl和咖啡因诱导的收缩的类似松弛反应。总之，Rhy和Isorhy的血管舒张作用在很大程度上与内皮无关，并由L型Ca2 + 通道介导。在较高浓度下，它们也会影响其他Ca2 +处理途径，尽管程度较小。虽然在KCl或激动剂（PE和U46619）引起的收缩方面，这两种异构体之间没有区别，但在咖啡因和CPA引起的收缩中，Rhy和Isorhy之间存在差异。

著录项

相似文献

  • 外文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号