西洋参茎叶皂甙的心血管药理研究进展

西洋参茎叶皂甙的心血管药理研究进展吕忠智，睢大篑（白求恩医科大学药理教研室，长春１３００２１）中国图书分类号Ｒ９７２西洋参（ＰａｎａｘｑｕｉｎｑｕｅｆｏｌｉｕｍＬｉｎｎ）属五加科，原产于美国，加拿大，现已在我国大面积引种成功。为综合利用西洋参资源，我...     

国产西洋参茎叶皂甙减轻四氯化碳致大鼠肝损伤

本文采用四氯化碳(CCl_4)肝损伤大鼠模型,观察了国产西洋参茎叶皂甙(PQS)对大鼠肝损害的影响。结果表明:国产西洋参茎叶皂甙降低血清丙氨酸转氨酶(ALT)的活性,使肝糖原含量,谷胱甘肽过氧化物酶活性回升,丙二醛(MDA)含量下降。证实国产西洋参茎叶皂甙可以减轻四氯化碳致大鼠肝损伤。。     

西洋参茎叶皂甙在阿霉素诱导大鼠心肌损伤中的抗氧化作用

西洋参茎叶皂甙50和100mg·kg~(-1)能明显降低阿霉素诱导的大鼠全血和心肌组织中丙二醛含量,保护超氧化物歧化酶及谷胱甘肽过氧化物酶活性。表明西洋参茎叶皂甙有抗氧化作用。     

中国人参与西洋参皂甙抗热应激作用的比较

中国红参根皂甙、中国人参茎叶皂甙和西洋参根皂甙在热应激的警觉期能抑制小鼠直肠温度的升高。用回归直线方程法比较了三种皂甙的抗热应激作用的半数致死时间(LT_(50)),中国红参根皂甙及茎叶皂甙的 LT_(50)均显著长于对照组,故能延长动物在热环境中的存活时间,而西洋参则无此作用。     

西洋参茎叶皂甙单体P－F_（11）对培养大鼠心肌细胞动作电位的作用

从西洋参茎叶皂甙中分离提取的Ｐｓｅｕｄｏｇｉｎｓｅｎｏｓｉｄｅ－Ｆ１１（３、１０、３０ｍｇ·Ｌ－１，Ｐ－Ｆ１１）使培养的Ｗｉｓｔａｒ大鼠心肌细胞动作电位的幅值、动作电位时程、阈电位、最大舒张电位、０期最大除极速率和复极１０％、５０％水平的动作电位时程剂量依赖性增大。Ｐ－Ｆ１１（１０ｍｇ·Ｌ－１）的作用可被维拉帕米（２μｍｏｌ·Ｌ－１）所对抗，Ｐ－Ｆ１１（３０ｍｇ·Ｌ－１）与ＢａｙＫ８６４４（０．７５ｍｍｏｌ·Ｌ－１）比较对心肌细胞动作电位的电参数的作用相似。实验结果表明，Ｐ－Ｆ１１可能具有钙通道激活作用。     

国产西洋参茎叶皂甙对老年大鼠组织及红细胞中SOD的影响

本实验观察了国产西洋参茎叶皂甙对老年大鼠组织和红细胞中SOD的作用。结果表明,国产西洋参茎叶皂甙100mg/kg能明显提高老年大鼠组织和红细胞中SOD的活性,与对照组相比有显著性差异(P<0.01)。同样剂量对青年大鼠SOD的活性无明显作用。     

加拿大产西洋参茎叶中的新三萜皂苷—西洋参皂苷L2

加拿大产西洋参茎叶中的新三萜皂苷———西洋参皂苷Ｌ２王金辉１）李铣（沈阳药科大学天然药物研究室，沈阳１１００１５）李文（沈阳药科大学分析测试中心，沈阳１１００１５）曾报道从加拿大产西洋参茎叶中分离得到了一个新的三萜皂苷———西洋参皂苷Ｌ１〔１〕．通过...     

西洋参茎叶皂甙单体P－F_（11）对培养大鼠心肌细胞动作电位的作用

从西洋参茎叶皂甙中分离提取的Ｐｓｅｕｄｏｇｉｎｓｅｎｏｓｉｄｅ－Ｆ１１（３、１０、３０ｍｇ·Ｌ－１，Ｐ－Ｆ１１）使培养的Ｗｉｓｔａｒ大鼠心肌细胞动作电位的幅值、动作电位时程、阈电位、最大舒张电位、０期最大除极速率和复极１０％、５０％水平的动作电位时程剂量依赖性增大。Ｐ－Ｆ１１（１０ｍｇ·Ｌ－１）的作用可被维拉帕米（２μｍｏｌ·Ｌ－１）所对抗，Ｐ－Ｆ１１（３０ｍｇ·Ｌ－１）与ＢａｙＫ８６４４（０．７５ｍｍｏｌ·Ｌ－１）比较对心肌细胞动作电位的电参数的作用相似。实验结果表明，Ｐ－Ｆ１１可能具有钙通道激活作用。     

西洋参茎叶皂甙对离体免疫左房肌生理特性的影响

西洋参茎叶皂甙对离体左房肌甙有显著的负性肌力作用，降低心肌兴奋性，延长功能不应期，对因氯化钡诱发的自律性有抑制作用。     

加拿大产西洋参茎叶中一种ionol型葡萄糖苷

利用大孔树脂、硅胶柱色谱及ＨＰＬＣ反相柱色谱法，从加拿大产西洋参（ＰａｎａｘｑｕｉｎｑｕｅｆｏｌｉｕｍＬ．）茎叶水提液的正丁醇萃取部分分离得到了一种ｉｏｎｏｌ型葡萄糖苷（１），根据其理化性质分析和光谱解析鉴定其为ｌｉｎａｒｉｏｎｏｓｉｄｅＡ，ｉｏｎ...     

Evidence for the site of action of glycerol trinitrate and diltiazem in inhibiting vasoconstrictor responses to norepinephrine in isolated renal arteries

The inhibitory effects of glycerol trinitrate (GTN) and diltiazem (DZ) on contractions produced by submaximal concentrations (ED 75) of norepinephrine (NE) and potassium chloride (KCl) were studied in isolated canine renal artery rings. In addition, the site of action of these compounds in blocking NE-induced contractions was determined by using zero calcium (Ca++) buffer + 2 mM EGTA (calcium-free solution). GTN was more potent than DZ in relaxing KCl-induced contractions (potential-operated calcium channels) as well as NE-induced contractions (receptor-operated calcium channels). In a Ca++-free buffer, the response to NE was reduced to approximately 20-25% of the response in normal Ca++ (1.25 mM) buffer. GTN (1 X 10(-9)-1 X 10(-4) M) produced a marked inhibition of NE-induced contractions in Ca++-free buffer, whereas DZ had no inhibitory effect even at very high concentrations (1 X 10(-4) M). Thus, GTN and DZ appear to interfere with different components of Ca++ entry through slow channels and intracellular Ca++ release. DZ primarily blocks the influx of Ca++ from the extracellular space, whereas GTN appears to act by inhibiting Ca++ movements at an intracellular site.     

Differences between rat and guinea pig aorta in postreceptor mechanisms of alpha 1-adrenoceptors.

The relative importance of different postreceptor mechanisms associated with alpha 1-adrenoceptor activation in guinea pig aorta and rat aorta was compared. In both tissues, a concentration-dependent correlation was observed between contractile responses produced by high concentrations of norepinephrine (NE) and inositol-1-phosphate (IP1) accumulation. Blockade of Ca2+ entry through voltage-dependent membrane channels by nifedipine had no inhibitory action on NE-induced contractile responses in guinea pig aorta, but significantly inhibited NE-induced contractile responses in rat aorta. Nifedipine had no major effect on NE-induced IP1 accumulation in either tissue. A medium with no Ca2+ inhibited NE-induced contractile responses and IP1 accumulation in guinea pig aorta, but had a more marked effect on contractile responses and IP1 accumulation in rat aorta. The combination of a high concentration of nifedipine and a medium with no Ca2+ almost completely inhibited NE-induced contractile responses and IP1 accumulation in both tissues. Exposure to EGTA also virtually completely inhibited NE-induced contractile response and IP1 accumulation in both tissues. Significant 45Ca2+ entry was stimulated in rat aorta by NE, and this entry was completely blocked by nifedipine. No significant 45Ca2+ entry was stimulated by NE in guinea pig aorta. We conclude that the most important postreceptor event linked to alpha 1-adrenoceptor stimulation in guinea pig aorta is activation of the phosphatidylinositol pathway, whereas in rat aorta Ca2+ entry through voltage-dependent membrane channels is as important as activation of the phosphatidylinositol pathway. We also conclude that activation of the phosphatidylinositol pathway in both tissues is critically dependent on the presence of a small amount of Ca2+, which may enter from the external medium.     

The calcium-related basis of action of adenosine in rabbit aortic smooth muscle

1. In rabbit aortic smooth muscle, adenosine inhibited the increase induced by norepinephrine (NE) in 45Ca uptake in the presence of KCl (under low affinity Ca2+ uptake conditions) and the NE-induced decrease in 45Ca uptake (under high affinity Ca2+ uptake conditions). Basal 45Ca uptake and KCl-stimulated 45Ca uptake were not altered by adenosine. 2. Adenosine blocked the NE-induced contraction (in high K+) and inhibited both the tonic and phasic components of the NE-induced contraction. 3. Thus, adenosine selectively inhibits release of the intracellular Ca2+ store important for the phasic response to NE and that Ca2+ uptake component important for the NE-induced tonic response.     

Dibutyryl cyclic AMP and forskolin inhibit phosphatidylinositol hydrolysis, Ca2+ influx and contraction in vascular smooth muscle.

Dibutyryl cyclic AMP and forskolin inhibited the contraction induced by norepinephrine (NE) more strongly than the high K(+)-induced contraction in isolated rat aorta. These inhibitors inhibited the 45Ca2+ influx stimulated by NE but not that by high K+, and they inhibited NE-induced inositol monophosphate accumulation. These results suggest that cAMP inhibits NE-induced contraction, at least partly, by inhibiting the alpha-adrenoceptor-mediated signal transduction and high K(+)-induced contraction by decreasing Ca2+ sensitivity but not Ca2+ influx.     

Potentiation by aminoethylisothiourea of the extra-cellular Ca(2+) component of norepinephrine-induced contraction in rat femoral arteries

Aminoethylisothiourea (AET) is a potent inhibitor of inducible nitric oxide synthase (NOS). The present study was performed to investigate whether AET and its rearrangement products might modulate vascular contraction independently of its effects as a NOS inhibitor in rat small femoral arteries. AET caused an endothelium-independent increase in contraction induced by norepinephrine (NE). This effect was not affected by either N(omega)-nitro-L-arginine methyl ester, nitro-L-arginine, indomethacin or propanolol, but it was suppressed in Ca(2+)-free medium. AET enhanced extracellular Ca(2+) component of NE-induced contraction, and this effect was prevented by the receptor-mediated Ca(2+) entry blocker, 1-{beta-[3-(p-methoxyphenyl)-propyloxyl]-p-methoxyphenetyl}- 1H-imidaz ole hydrochloride (SK&F 96365), but not by the voltage-dependent Ca(2+) channel blocker, nitrendipine. AET did not alter the response to CaCl(2) in vessels exposed to KCl depolarization. The protein kinase C (PKC) inhibitor, 2-[1-(3-dimethylaminopropyl)indol-3-yl]-3-(indol-3-yl) (GF 109203X), prevented the potentiating effect of AET on the NE response. AET failed to produce an increase in tone in the presence of NE and GTP in permeabilized arteries. Among the AET rearrangement products, mercaptoethylguanidine produced an endothelium-independent increase in the NE response. 2-aminothiazoline had no effect, and guanidinoethyldisulphide produced relaxation. The effect of mercaptoethylguanidine was dependent on extracellular Ca(+) and was prevented by GF 109203X. These results indicate that AET is able to potentiate the contraction to NE in rat femoral resistance arteries independently of its inhibitory effect on either NOS or cyclo-oxygenase. Its effect occurs via an enhancement of SK&F 96365-sensitive Ca(2+) entry. A PKC inhibitor-sensitive mechanism also appears to be involved in the AET effect. Mercaptoethylguanidine potentiates NE response through a mechanism similar to AET.     

Vasorelaxant effects of methyl brevifolincarboxylate from the leaves of Phyllanthus niruri

Methyl brevifolincarboxylate (1) isolated from the leaves of Phyllanthus niruri L. showed a vasorelaxant effect on rat aortic rings. Compound 1 exhibited slow relaxation activity against norepinephrine (NE)-induced contractions of rat aorta with or without endothelium. The compound did not affect contractions induced by a high concentration (60 mM) of K+, whereas it inhibited NE-induced vasocontraction in the presence of nicardipine. These results suggest that the inhibition of NE-induced vasocontraction by compound 1 is in part attributable to a decrease in [Ca2+]i through receptor-operated Ca2+ channels.     

Effects of nitroprusside and D 600 on norepinephrine- and KCl-stimulated Ca++ activation and contraction systems in canine renal vein as compared to canine renal artery

The effects of nitroprusside (NP) and D 600 on norepinephrine (NE)- and KCl-induced maximal contractions and unstimulated 45Ca uptake and efflux were delineated in canine renal vein (CRV) and compared with results in renal artery. In CRV, but not in renal artery, NE-induced contractions are usually associated with rhythmic oscillations in developed tension. Corresponding KCl-induced contractions are not associated with rhythmic activity and are depressed by 57% in the presence of phentolamine (PA). The calcium channel blocker, D 600, rapidly and extensively relaxed NE-induced contractions (86%) in CRV, but slowly and moderately relaxed similar responses in artery (46%). PA-resistant, KCl-induced contractions were equally sensitive to the relaxant effects of D 600 in CRV (73%) or artery (72%), but the rate of relaxation was much more rapid in CRV. Prior exposure to D 600 inhibited KCl-induced contractions in both CRV and artery (99 versus 91%, respectively). Similar prior treatment reduced NE-induced contractions (60%) in CRV, and prevented the development of any NE-dependent rhythmic activity. In renal artery, NE-induced contractions were unaffected by prior D 600 exposure. NP relaxed KCl-induced contractions 32% in the presence of PA in CRV, but had little effect on KCl-induced responses in artery (6%). Prior exposure to NP inhibited KCl-induced contractions 60-67% in CRV, which is approximately twice the inhibition seen in artery (31%). Relaxation of NE-induced contractions with NP in CRV and renal artery are (43% and 38%, respectively) approximately equal. In renal artery, responses to NE are less sensitive (1.6-fold) to prior NP exposure than in CRV. Prior exposure to NP or to NP plus D 600 reduced NE-induced contractions in CRV 37% and 96%, respectively. NP and D 600 were without effect on unstimulated 45Ca uptake in CRV. In CRV, D 600 had no effect on 45Ca efflux into a O-Ca++ solution, whereas NP decreased the rate of 45Ca efflux in a maintained manner. Thus, NP and D 600 appear to interfere with differing components of Ca++ entry and Ca++ release in CRV. However, these components are less readily differentiated and more interdependent than similar, well-defined and characterized components in arterial smooth muscle, and appear to be convergent.     

Ca^2＋ participates in α1B-adrenoceptor-mediated cAMP response in HEK293 cells

AIM: To investigate the alpha1B-adrenoceptor (alpha1B-AR)-mediated cAMP response and underlying mechanisms in HEK293 cells. METHODS: Full-length cDNA encoding alpha1B-AR was transfected into HEK293 cells using the calcium phosphate precipitation method, and alpha1B-AR expression and cAMP accumulation were determined by using the saturation radioligand binding assay and ion-exchange chromatography, respectively. RESULTS: Under agonist stimulation, alpha1B-AR mediated cAMP synthesis in HEK293 cells, and blockade by PLC-PKC or tyrosine kinase did not reduce cAMP accumulation induced by NE. Pretreatment with pertussis toxin (PTX) had little effect on basal cAMP accumulation as well as norepinephrine (NE)-stimulated cAMP accumulation. In addition, pretreatment with cholera toxin (CTX) neither mimicked nor blocked the effect induced by NE. The extracellular Ca2+ chelator egtazic acid (EGTA), nonselective Ca2+ channel blocker CdCl2 and calmodulin (CaM) inhibitor W-7 significantly reduced NE-induced cAMP accumulation from 1.59%+/-0.47% to 1.00%+/-0.31%, 0.78%+/-0.23%, and 0.90%+/-0.40%, respectively. CONCLUSION: By coupling with a PTX-insensitive G protein, alpha1BAR promotes Ca2+ influx via receptor-dependent Ca2+ channels, then Ca2+ is linked to CaM to form a Ca2+-CaM complex, which stimulates adenylyl cyclase (AC), thereby increasing the cAMP production in HEK293 cell lines.     

Influence of norepinephrine on the tonic and phasic depression of Vmax by nifedipine and verapamil in guinea pig ventricle

Right ventricular strips from guinea pig hearts were used to study the interaction between norepinephrine (NE) and the Ca2+ channel blockers nifedipine and verapamil on maximal upstroke velocity (Vmax) of rapid depolarization in potassium-depolarized preparations. Barium ion (0.8 mM) was added to the bathing solution to restore excitability of the K+-depolarized tissue. Concentrations of verapamil (5 X 10(-7) M) and nifedipine (5 X 10(-8) M) were selected to produce optimal depression of Vmax under both tonic (rested) and phasic (pacing frequencies from 0.05 to 2.0 Hz) conditions. NE increased the tonic and phasic Vmax of control preparations in equal proportion at all stimulation frequencies. Thus, the physiological frequency dependence of Vmax was not altered by NE. NE (10(-6) M) produced an increase of 11.8 +/- 2.2% in the tonic Vmax of verapamil-treated preparations and an increase of 17.4 +/- 1.1% in the tonic Vmax of nifedipine-treated preparations. In each case the enhancement of Vmax by NE was proportional for both tonic and phasic conditions, thus showing no effect on the frequency-dependent action of either drug. In all cases, the NE-induced increase in Vmax was concentration dependent. Higher concentrations of NE thwarted the measurement of tonic Vmax due to the onset of spontaneous activity except in the presence of nifedipine (5 X 10(-8) M). The maximal concentration of NE that could be tolerated without the onset of spontaneous activity was directly related to the degree of tonic depression of Vmax induced by the Ca2+ channel blocking agent.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of G(i)-proteins in norepinephrine-mediated vasoconstriction in rat tail artery smooth muscle

We showed, in rat de-endothelialised tail artery, that pertussis toxin (PTX) (1 microg/mL, 2 hr) attenuated norepinephrine (NE)-induced vasoconstriction without modifying intracellular calcium concentration [Ca2+](i) mobilisation. We suggested the existence of two NE-induced intracellular pathways: a first, which would be insensitive to PTX and lead to [Ca2+](i) mobilisation, and a second sensitive to PTX and involved in the [Ca2+](i) sensitivity of NE-induced contraction. The aim of this study was to demonstrate the existence of the second intracellular pathway. PTX-sensitive G(i/o)-proteins in rat tail artery SMC membrane were identified by immunoblot and ADP-ribosylation. [(32)P]ADP-ribosylation of alpha(i/o)-subunits was demonstrated in situ by perfusing rat de-endothelialised tail artery segments with PTX (1 microg/mL, 2 hr), which suggested that G(i/o)-protein inactivation was involved in the reduction by PTX of the [Ca2+](i) sensitivity of NE-induced contraction. Coupling between G(i/o)-proteins and NE receptors was confirmed by the NE-induced increase in G(i/o)-specific GTPase activity (24.1 +/- 1.9 vs 8.8 +/- 0.4 pmol P(i)/mg protein at 5 min; P < 0.05 vs basal). [(3)H]Prazosin-binding data showed the presence of a heterogeneous alpha(1)-AR population in rat tail artery smooth muscle cells. We demonstrated the in vitro coupling between alpha(1A)-AR subtype and alpha(i)-subunits. In conclusion, we identified, in rat de-endothelialised tail artery, a PTX-sensitive G(i/o)-protein-modulated pathway that is coupled to NE receptors via alpha(1A)-AR. We suggest that NE stimulates two alpha(1)-AR-mediated intracellular pathways: a first, which is mediated by a G(q)-protein and leads to [Ca2+](i) mobilisation and contraction, and a second, which is mediated by a G(i)-protein and is involved in the amplification of the [Ca2+](i) sensitivity of NE-induced tension.