粉防己碱，钩藤碱和维拉帕米对兔主动脉平滑肌细胞内外钙转运的作用

粉防己碱和钩藤碱对由高钾和去甲肾上腺素引起的兔主动脉条收缩的抑制作用没有维拉帕米强。粉防己碱，钩藤碱和维拉帕米在由去甲肾上腺素和５－羟色胺引起的两相收缩中，抑制Ⅰ相收缩的ＩＣ５０小于抑制Ⅱ相收缩的ＩＣ５０．粉防己碱，钩藤碱抑制由去甲肾上腺素引起的Ⅰ相收缩的ＩＣ５０分别是抑制高钾所致收缩的１／１２．８和１／６．但维拉帕米没有表现此种关系，三种药物均不能对抗卡西霉素引起的收缩。粉防己碱和钩藤碱能增强咖啡因所致收缩，但维拉帕米抑制之，这些结果表明粉防己碱和钧藤碱为细胞内钙动员抑制剂，而且它们的作用点不同于维拉帕米。     

异莲心碱对麻醉大鼠血流动力学及平滑肌收缩反应的影响

异莲心碱2.5-10 mg·kg^-1 iv可剂量依赖性地一过性轻度降低麻醉大鼠心率, 收缩动脉压, 平均动脉压, 舒张动脉压, 左室收缩压, 左室压力最大变化速率,而对左室舒张末压无显著影响. 异莲心碱使甲氧明所致兔主动脉环和大鼠肛尾肌收缩的量 效曲线平行右移,最大反应不降低,pA₂分别为6.25和6.15,对高K⁺所致兔主动脉环收缩也有明显抑制作用. 异莲心碱还明显抑制去甲肾上腺素引起的兔主动脉环依内钙和外钙的收缩反应. 结果表明,异莲心碱对α₁受体有较为明显的阻断作用,并可抑制该受体引起的内钙释放和外钙内流,对电压依赖性钙通道也有阻滞作用. 异莲心碱的一过性轻度降压和抗心律失常作用可能与这些均有关.     

甲基莲心碱对大鼠心电图和蟾蜍坐骨神经动作电位的影响

在麻醉大鼠观察了恒速iv甲基莲心碱对ECG的影响,并与奎尼丁和粉防己碱进行了对比性研究。甲基莲心碱对大鼠ECG的影响与奎尼丁相似,剂量(2～40mg/kg)依赖性地延长P-R和Q-T,使QRS增宽;粉防己碱不增宽QRS。结果显示甲基莲心碱作用机理与奎尼丁相似,不同于粉防己碱。甲基莲心碱与奎尼丁都可依浓度抑制蟾蜍坐骨神经APA,二者作用强度相近。     

二乙酰基莲心碱对猪冠状动脉条的影响

目的:观察二乙酰基莲心碱拮抗氯化钾、乙酰胆碱(Ach)和组胺(His)所致猪冠状动脉条收缩的作用.方法:离体平滑肌实验方法,观察二乙酰基莲心碱对氯化钾,Ach,His所致猪冠状动脉条收缩曲线的影响以及在无钙克氏液中,对His引起猪冠状动脉条第一相收缩和钙引起第二相收缩的影响.结果:不同剂量二乙酰基莲心碱可使氯化钾,Ach,His所致冠脉条收缩量效曲线呈非竞争性拮抗作用,对冠脉条第一相和第二相收缩都有明显的抑制作用结论:二乙酰基莲心碱具有扩张冠脉的作用,此作用与拮抗细胞内钙的释放和抑制外钙内流有关.     

甲基莲心碱和异莲心碱对5α-还原酶抑制作用的研究

摘 要 目的： 观察甲基莲心碱和异莲心碱对5α 还原酶的抑制作用,为开发5α-还原酶抑制药提供参考依据。方法: 设置不同反应管和对照管,将肝脏匀浆液、还原性辅酶II（NADPH）、睾酮、待测样品、阳性对照药及缓冲液分别加入到96孔板中,借助酶标仪,测定340 nm处1 h内NADPH的吸光度变化值,空白对照组与实验组比较,计算受试药物对5α-还原酶的抑制率大小。结果: 在实验设定的6个浓度梯度（2~40 mg·mL^-1）中,甲基莲心碱和异莲心碱最佳的抑制作用浓度均为10 mg·mL^-1,抑制率分别为(25.00±1.030)%和(29.90±2.410)%;与空白组相比,甲基莲心碱和异莲心碱表现出明显的5α-还原酶抑制作用（P<0.05）;同浓度（10 mg·mL^-1）下,甲基莲心碱和异莲心碱对5α 还原酶抑制作用低于阳性对照组（P<0.05）;与甲基莲心碱相比,异莲心碱对5α 还原酶抑制作用更显著（P<0.05）。结论:甲基莲心碱和异莲心碱对5α 还原酶有较强抑制作用,在治疗良性前列腺增生疾病方面,有一定的应用前景。     

粉防己碱、甲基莲心碱和蝙蝠葛碱增强长春新碱诱导人乳腺癌MCF-7多药耐药细胞凋亡

目的　观察粉防己碱、甲基莲心碱和蝙蝠葛碱与长春新碱合用对多药耐药肿瘤细胞诱导凋亡的作用。方法　采用荧光染料Hoechst33342和碘化丙锭联染技术、流式细胞术和琼脂糖凝胶电泳技术,检测长春新碱及其与上述单体合用诱导耐药株瘤细胞MCF-7/Dox的凋亡程度。结果　单用长春新碱可引起约10%细胞凋亡,而长春新碱与粉防己碱、甲基莲心碱或蝙蝠葛碱合用明显地增加细胞凋亡的百分率,其中粉防己碱的作用最强。联合用药的细胞凋亡数显著地大于单用长春新碱的作用。结论　粉防己碱、甲基莲心碱和蝙蝠葛碱均有明显的增强长春新碱诱导人乳腺癌MCF-7多药耐药细胞的凋亡作用。     

粉防己碱、甲基莲心碱和蝙蝠葛碱增强长春新碱诱导人乳腺癌MCF-7多药耐药细胞凋亡

目的　观察粉防己碱、甲基莲心碱和蝙蝠葛碱与长春新碱合用对多药耐药肿瘤细胞诱导凋亡的作用。方法　采用荧光染料Hoechst 33342和碘化丙锭联染技术、流式细胞术和琼脂糖凝胶电泳技术 ,检测长春新碱及其与上述单体合用诱导耐药株瘤细胞MCF 7/Dox的凋亡程度。结果　单用长春新碱可引起约 10 %细胞凋亡 ,而长春新碱与粉防己碱、甲基莲心碱或蝙蝠葛碱合用明显地增加细胞凋亡的百分率 ,其中粉防己碱的作用最强。联合用药的细胞凋亡数显著地大于单用长春新碱的作用。结论　粉防己碱、甲基莲心碱和蝙蝠葛碱均有明显的增强长春新碱诱导人乳腺癌MCF 7多药耐药细胞的凋亡作用     

甲基莲心碱降低血压及松弛血管作用的分析

甲基莲心碱(neferine,Nef)对自发性高血压大鼠有明显的降压作用,ig给药降压作用可维持3h以上。对由高钾去极化引起的兔主动脉环收缩的抑制作用为维拉帕米(verapamil,Ver)的1/792,使CaCl_2及甲氧明(methoxamine,Met)的量效曲线平行右移,最大反应前者压低、后者不变,pD_2及pA_2值分别为5.4及6.3。还抑制由去甲肾上腺素(norepinephrine,NE)引起的依内钙收缩反应,提示Nef对α_1肾上腺素受体有阻断作用及较弱的钙拮抗作用。     

莲心碱二乙醚对猪冠状动脉条的影响

目的观察莲心碱二乙醚拮抗KCl，乙酰胆碱（Ach）和组胺（Hist）所致猪冠状动脉条收缩的作用。方法离体平滑肌实验方法，观察莲心碱二乙醚对KCl，Ach，Hist所致猪冠状动脉条收缩曲线的影响以及在无Ca²⁺克氏液中，对Hist引起猪冠状动脉条第一相收缩和Ca²⁺引起第二相收缩的影响。结果不同剂量莲心碱二乙醚可使KCl，Ach，Hist所致冠脉条收缩量效曲线呈非竞争性拮抗作用，对冠脉条第一相和第二相收缩都有明显的抑制作用。结论莲心碱二乙醚具有扩张冠脉的作用，此作用与拮抗细胞内钙的释放和抑制外钙内流有关。     

粉防己化学成分氧化防己碱和防己菲碱的化学结构

从防已科植物粉防己(Stephania tetrandra S.Moore)的干燥块根中分离到五种结晶。其中三种鉴定为粉防己碱(tetrandrine,晶Ⅱ),防己诺林碱(fangehinoline,晶Ⅳ)和轮环藤酚碱(cyclanoline,晶Ⅴ)。晶Ⅰ和晶Ⅲ为新生物碱,其结构经光谱分析推定为Ⅰ和Ⅲ,结构Ⅱ已由X射线衍射实验证实,并分别命名为氧化防己碱(oxofangchirine)和防己菲碱(stephanthrine).     

双苄基异喹啉类生物碱的心血管药理作用

Tetrandrine, dauricine, daurisoline and neferine are bisbenzylisoquinoline alkaloid derivatives isolated from Chinese traditional medicine and herbs. The cardiovascular pharmacological effects and the mechanism of actions of these compounds were reviewed. Tetrandrine isolated from Stephania tetrandra S Moore possesses antihyper-tensive and antiarrhythmic effects. The antihypertensive effects of tetrandrine have been demonstrated in experi-mental hypertensive animals and in hypertensive patients. Recent studies showed that in addition to its calcium antagonistic effect, tetrandrine interacted with M receptors. Modulation by M receptor is one of the pharmacologi-cal mechanisms of cardiovascular effects of tetrandrine. Dauricine and daurisoloine were isolated from Menispermum dauricum DC. The antiarrhythmic effects of dauricine have been verified in different experimental arrhythmic models and in cardiac arrhythmic patients. Dauricine blocked the cardiac transmembrane Na ,K and Ca2 ion currents. Differin     

Development of a cell-based HTS adaptable calcium fluorescent assay in FlexStation3 for the screening of TRPV3 inhibitors

To develop a cell-based high-throughput calcium fluorescent assay for screening of TRPV3 channel modulators, we employed the FlexStation3 microplate reader and optimized conditions of the high-throughput screening (HTS) adaptable calcium fluorescent assay, such as cell density, incubation time and concentration of Cal-520 calcium fluorescent dye. The optimized FlexStation3 assay included the cell density of 40 000 cells per well, 5.0% of Cal-520 calcium fluorescent dye and 1.5 h of incubation time. Using the FlexStation3 assay in a 96-well format, we screened and identified a natural neferine from Nymphaeaceae plant that inhibited TRPV3 channel. To further confirm the inhibitory effect of neferine on TRPV3, we utilized the whole-cell patch clamp recordings and determined the dose-dependent inhibition of TRPV3 current by neferine with an IC₅₀ at 24.5±4.1 μM (n = 6) without inhibition of TRPV1 or TRPV4 channels. Taken together, our data showed that this validated HTS adaptable calcium fluorescent assay in FlexStation3 format could be used for screening and identification of modulators for either TRPV3 channel or other calcium permeable TRP channels. The identified natural neferine could be used as a tool for pharmacological investigations of TRPV3 channel function.     

PY 108-068, a new, potent, and selective inhibitor of calcium-induced contraction of rabbit aortic rings

PY 108-068 (PY) is a new benzoxadiazolyle dihydropyridine derivative. It potently antagonizes calcium-induced contractions of rabbit aorta in depolarizing solution (PD'2:8.8). This antagonism is selective, since no relevant antagonistic effects against noradrenaline (NA)-, serotonin (5-HT)-, and angiotensin II (AII)-induced contractions are found at the highest concentration of PY (10(-5) M). Verapamil (V), examined for comparison, was less selective with respect to its antagonism: pA2 value against calcium-induced contractions in depolarizing solution: 7.6, pA2 against serotonin-induced contractions: 6.9. In calcium-free Krebs--Henseleit solution tachyphylaxis occurred after three to four administrations of NA, 5-HT, or AII. When calcium was added in the presence of one of these agonists, the slow phase of concentration, which depends on extracellular calcium, developed. This slow phase of contraction was not inhibited to a relevant extent by a 10(-5) M concentration of PY. Verapamil inhibited the tonic contraction induced by serotonin (pD'2: 5.5) but not to a relevant extent the contractions induced by the two other agonists. PY therefore, inhibits calcium-induced contractions of rabbit aorta in depolarizing solution very selectively, and shows hardly any effects on receptor-operated channels.     

Effects of tetrandrine on smooth muscle contraction induced by mediators in pulmonary hypertension

AIM: In attempt to characterize tetrandrine on pulmonary hypertension, biological activities induced by a range of mediators implicated in the pathogenesis of pulmonary hypertension were investigated. METHODS: Pulmonary artery rings and tracheal segments were contracted with couples of bioactive substances in which a series experi-ments including effects of tetrandrine on calcium agonist, endothelin, thromboxane A2, angiotensin II, neuropeptide Y, histamine, 5-methyl furmethide were performed, the influences of tetrandrine in the concentration of 1 to 30 μmol/L were investigated. RESULTS: Tetrandrine inhibited calcium agonist BayK8644, endothelin-1 and throm-boxane A2 mimetic U46619, angiotensin II- and neuropeptide Y-induced contractile responses with depression of the maximal contraction of pulmonary artery rings in a varying extent. Tetrandrine inhibited leukotriene E4-induced concentration-response curve in a competitive antagonist manner with a pKB of (5.29 ±0.11) without any influence leukotrien     

粉防己碱对大鼠离体主动脉条45Ca内流的影响

本文研究了粉防己碱（Ｔｅｔｒａｄｒｉｎｅ，Ｔｅｔ）对大鼠离体胸主动脉条~（４５）Ｃａ内流的影响。结果表明，粉防己碱（３×１０~（－５）ｍｏｌ·Ｌ~（－１））与维拉帕米（Ｖｅｒａｐａｍｉｌ，浓度为１×１０~（－５）ｍｏｌ·Ｌ~（－１））相似，可以抑制高Ｋ~＋激发的主动脉条~（４５）Ｃａ的内流量，但不能阻断由苯肾上腺素（Ｐｈｅｎｙｌｅｐｈｒｉｎｅ，浓度为１×１０~（－５）ｍｏｌ·Ｌ~（－１））激发的~（４５）Ｃａ内流量。结果提示，粉防己碱可能是选择性地阻断电压操纵的钙通道而抑制~（４５）Ｃａ内流。     

Tetrandrine: A novel calcium channel antagonist inhibits type I calcium channels in neuroblastoma cells

Tetrandrine, an alkaloid isolated from the Chinese herb, Radix stephaniae tetrandrae, has been used clinically as a hypotensive agent for a long time. Recently, several studies have demonstrated that tetrandrine behaves like a calcium entry blocker. In the present investigation, the whole cell version of the patch clamp technique was used to study the effect of tetrandrine on the type I (transient inward) calcium current in neuroblastoma cells. These results showed that tetrandrine inhibited the transient inward current, without affecting the channel kinetics. The effects of tetrandrine were dose-dependent and reversible but did not depend on the frequency of stimulation (use-dependence) or the membrane potential. These data clearly demonstrate that tetrandrine is a novel and potent antagonist of the transient inward current in neuroblastoma cells.     

Differential blockade of alpha,beta-methylene-ATP, noradrenaline and electrically evoked contractions of the rat vas deferens

The present study was carried out compare the effects of nifedipine, verapamil, papaverine and chloroethylclonidine (CEC) on the electrically-induced contractions and on the contractions produced by exogenous noradrenaline and alpha, beta methylene-ATP in the epidydimal portion of rat vas deferens. Nifedipine inhibited in a concentration-dependent fashion the purinergic component (phase I) of the electrically evoked response. Verapamil (10(-7) M-10(-5) M) did not inhibit significantly or even potentiated phase I of the contractile response to single-pulse field stimulation but inhibited the response to alpha,beta methylene-ATP. Papaverine left unaffected phase I but depressed the response to alpha,beta methylene-ATP. CEC significantly potentiated the purinergic component of the electrically-evoked response and the response induced by alpha,beta methylene-ATP. Nifedipine was devoid of any inhibitory action on the noradrenergic component (phase II) of the response to single shock. Verapamil at the highest concentration used (10(-5) M) was able to partially inhibit phase II. Papaverine abolished in a concentration-dependent manner the noradrenergic component of the response to single shock. CEC abolished the phase II of single shock while was devoid of any inhibitory action on exogenous noradrenaline. The implications of these differences among the compounds studied in the present work are discussed in relation to roles of calcium channels.     

粉防己碱抑制中性粒细胞溶酶体酶释放与钙的关系

未耗竭中性粒细胞(Neutrophil,Neu)内钙,提高细胞外钙浓度可使β-葡萄糖醛酸酶(β-glucuronidase,β-G)释放增加;而耗竭钙后,βG释放则显著减少,复钙后又增加,但仍达不到未耗竭钙时的水平。提示细胞内、外钙均参与β-G释放,粉防已碱(Tetrandrine,Tet)和维拉帕米(Verapamil,Ver)均可抑制钙和经同种血清调理的酵母多糖引起的酶释放及KCl引起钙通道开放后导致的β-G释放增加,表明Tet抑制β-G释放的机理与其钙拮抗作用有关。