Fusi Fabio, Saponara Simona, Pessina Federica, Gorelli Beatrice, Sgaragli Giampietro
Istituto di Scienze Farmacologiche, Università degli Studi di Siena, via A. Moro 2, Italy.
Eur J Nutr. 2003 Jan;42(1):10-7. doi: 10.1007/s00394-003-0395-5.
Several studies have indicated that quercetin promotes relaxation of vascular smooth muscle both in vivo and in vitro. However, Saponara et al. [(2002) Br J Pharmacol 135: 1819-1827] have demonstrated that quercetin is an activator of vascular L-type Ca(2+) channels.
We investigated the mechanical and electrophysiological properties of quercetin and its rutoside, rutin, in an attempt to clarify how Ca(2+) channel activation might be related to the myorelaxing activity.
Aorta ring preparations and single tail artery myocytes were employed for functional and patch-clamp experiments, respectively.
Rutin was found to relax intact rat aorta rings, which had been precontracted with phenylephrine (pIC(50) = 5.65 +/- 0.31) but in contrast had no effect on depolarised (60 mM K(+)) preparations or on those from which the endothelium had been removed. Furthermore, rutin did not affect L-type Ca(2+) current recorded in rat tail artery myocytes. The quercetin-induced relaxation of intact rings precontracted with phenylephrine exhibited two components characterised by 6.23 +/- 0.38 and 4.66 +/- 0.09 pIC(50), respectively. Removal of the endothelium abolished the first component, leaving the second unaltered. Moreover, quercetin was found to relax 60 mM K(+) depolarised rings with a pIC(50) of 4.59 +/- 0.03. The application of quercetin in isolated smooth muscle cells brought about a marked increase of L-type Ca(2+) current (pEC(50) = 5.09 +/- 0.05). Unlike quercetin, Bay K 8644 contracted aorta rings preincubated with 10, 20 or 30 mM K(+). The myotonic effect of Bay K 8644 was observed both in the absence or presence of 30 microM quercetin. The application of Bay K 8644 (10-100 nM) caused a further significant increase in L-type Ca(2+) current in rat tail artery myocytes stimulated with 30 microM quercetin.
Quercetin is a naturally occurring L-type Ca(2+) channel agonist. This effect, however, is overwhelmed by quercetin-induced vasorelaxation taking place via pathways which are more relevant than L-type Ca(2+) influx in the hierarchy of functional competencies.
多项研究表明，槲皮素在体内和体外均能促进血管平滑肌舒张。然而，萨波纳拉等人[（2002年）《英国药理学期刊》135: 1819 - 1827]已证明槲皮素是血管L型钙通道的激活剂。
我们研究了槲皮素及其芦丁糖苷（芦丁）的机械和电生理特性，试图阐明钙通道激活与肌肉舒张活性之间可能存在的关系。
分别使用主动脉环标本和单尾动脉肌细胞进行功能实验和膜片钳实验。
发现芦丁可使预先用去氧肾上腺素预收缩的完整大鼠主动脉环舒张（pIC50 = 5.65 ± 0.31），但相反，对去极化（60 mM K +）标本或去除内皮的标本无影响。此外，芦丁不影响大鼠尾动脉肌细胞中记录的L型钙电流。槲皮素诱导的、预先用去氧肾上腺素预收缩的完整环的舒张表现出两个成分，其特征分别为pIC50为6.23 ± 0.38和4.66 ± 0.09。去除内皮消除了第一个成分，而第二个成分未改变。此外，发现槲皮素能使60 mM K +去极化的环舒张，pIC50为4.59 ± 0.03。在分离的平滑肌细胞中应用槲皮素导致L型钙电流显著增加（pEC50 = 5.09 ± 0.05）。与槲皮素不同，Bay K 8644使预先用10、20或30 mM K +预孵育的主动脉环收缩。在不存在或存在30 μM槲皮素的情况下均观察到Bay K 8644的强直性作用。应用Bay K 8644（10 - 100 nM）导致在用30 μM槲皮素刺激的大鼠尾动脉肌细胞中L型钙电流进一步显著增加。
槲皮素是一种天然存在的L型钙通道激动剂。然而，在功能能力层次结构中，这种作用被槲皮素通过比L型钙内流更相关的途径诱导的血管舒张所掩盖。
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