Shen Jia, Yip Siewting, Wang Zhixing, Wang Wei, Xing Dongming, Du Lijun
Protein Science Laboratory of the Ministry of Education, Laboratory of Pharmaceutical Sciences, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, China.
Eur J Pharmacol. 2008 Feb 12;580(3):366-71. doi: 10.1016/j.ejphar.2007.11.012. Epub 2007 Nov 17.
Brazilein (6a,7-dihydro-3,6a,10-trihydroxy-benz[b]indeno[1,2-d]pyran-9(6H)-one) is a compound isolated from Caesalpinia sappan. The vasoactivities of brazilein were evaluated in isolated rat thoracic aorta. The results showed that brazilein can dose-dependently induce contraction of rat thoracic aorta in the resting and phenylephrine pre-evoked state. The average response to 100 microM of brazilein was 30% of the 50 mM KCl contraction, 26% of the 10 muM phenylephrine and 116% of the 20 mM caffeine contraction in comparison. The effects of vasocontraction were proved not to be endothelial dependent and could not be inhibited by alpha-adrenergic receptor blocker phentolamine, beta-adrenergic receptor blocker propranolol, M-adrenaline receptor blocker atropine, angiotensin II receptor blocker losartan or the non-selective nitric oxide synthase (NOS) inhibitor NG-Nitro-L-Arginine Methyl Ester (L-NAME). However the influx of extracellular calcium seemed to be required for this action, because depletion of extracellular calcium and the addition of L-type calcium ion channel antagonist (nimodipine and diltiazem), calcium ion channel activator (BAY-K8644) and potassium ion channel opener (pinacidil) could significantly affect the contraction induced by brazilein. We also investigated the possible signal mechanisms underlying brazilein-induced contraction using selective inhibitors. The inhibitors of myosin light chain kinase (MLCK), Rho-kinase (ROK) and extracellular signal regulated kinase (ERK) can suppress the effect of brazilein respectively, whereas inhibitors of other signaling or receptor molecules such as protein kinase C (PKC) and inositol 1,4,5-triphosphate (IP3) receptor had no effect. All these results demonstrated that brazilein can induce contraction of rat aorta, that the Ca2+ influx, ROK and ERK signal pathways and MLCK activation must be involved in the contractile processes.
巴西苏木素（6a,7-二氢-3,6a,10-三羟基-苯并[b]茚并[1,2-d]吡喃-9(6H)-酮）是从苏木中分离得到的一种化合物。在离体大鼠胸主动脉中评估了巴西苏木素的血管活性。结果表明，巴西苏木素在静息状态和去氧肾上腺素预激发状态下均可剂量依赖性地诱导大鼠胸主动脉收缩。相比之下，100微摩尔巴西苏木素的平均反应分别为50毫摩尔氯化钾收缩反应的30%、10微摩尔去氧肾上腺素收缩反应的26%和20毫摩尔咖啡因收缩反应的116%。血管收缩作用被证明不依赖于内皮，且不能被α-肾上腺素能受体阻滞剂酚妥拉明、β-肾上腺素能受体阻滞剂普萘洛尔、M-肾上腺素能受体阻滞剂阿托品、血管紧张素II受体阻滞剂氯沙坦或非选择性一氧化氮合酶（NOS）抑制剂N-硝基-L-精氨酸甲酯（L-NAME）抑制。然而，这种作用似乎需要细胞外钙的内流，因为细胞外钙的耗尽以及添加L型钙离子通道拮抗剂（尼莫地平和地尔硫卓）、钙离子通道激活剂（BAY-K8644）和钾离子通道开放剂（匹那地尔）均可显著影响巴西苏木素诱导的收缩。我们还使用选择性抑制剂研究了巴西苏木素诱导收缩的可能信号机制。肌球蛋白轻链激酶（MLCK）、Rho激酶（ROK）和细胞外信号调节激酶（ERK）的抑制剂均可分别抑制巴西苏木素的作用，而其他信号或受体分子如蛋白激酶C（PKC）和肌醇1,4,5-三磷酸（IP3）受体的抑制剂则无作用。所有这些结果表明，巴西苏木素可诱导大鼠主动脉收缩，Ca2+内流、ROK和ERK信号通路以及MLCK激活必定参与了收缩过程。
