A dual action of papaverine on calcium uptake by microsomal fraction isolated from rat uterus

The effects of papaverine, cyclic AMP and MIX (3-isobutyl-1-methylxanthine, a phosphodiesterase inhibitor) on calcium uptake by a microsomal fraction from rat uterus were tested in the presence of 3 mM ATP. Papaverine potentiated calcium uptake in the presence of oxalate but inhibited it in the absence of oxalate. However, cyclic AMP and MIX did not influence calcium uptake, neither in the presence nor the absence of oxalate. These results suggest that calcium uptake by plasma membrane-derived vesicles in the absence of oxalate is inhibited by papaverine and that papaverine potentiated calcium uptake by the internal membranes in the presence of oxalate. They suggest also that the stimulatory action of papaverine involves a cyclic AMP-independent mechanism in addition to the mechanism via cyclic AMP.     

Stimulation of Na+,K+-ATPase of isolated smooth muscle membranes by the Ca2+ channel inhibitors,nimodipine and nitrendipine

Nimodipine (0.015 to 1.5 μM) increased Na⁺, K⁺-ATPase activity by 70–120% in isolated smooth muscle membranes. At 0.015 μM, nitrendipine, but not nifedipine, verapamil or diltiazem, also activated this enzyme. Nimodipine stimulated this Na⁺, K⁺ATPase three times more than nitrendipine at 15 nM. Marked stimulation of Na⁺,K⁺-ATPase by nimopidine was seen in membranes from rat and guinea pig aorta and rat vas deferens, but not in membranes from guinea pig heart or brain. Although it is not known whether these results are applicable to intact cells, the results are consistent with the hypothesis that vasodilation produced by nimodipine and nitrendipine may be due not only to inhibition of Ca²⁺ entry but also to the stimulation of the Na^? pump.     

谷氨酸对牛大脑中动脉平滑肌细胞胞浆静息Ca2+和ATP触发的Ca2+内流的影响

目的观察谷氨酸对牛大脑中动脉平滑肌细胞有无直接的激动作用以及对ATP触发的Ca2+内流有无影响?方法采用Fura-2荧光法测定胞浆内Ca2+变化技术,在培养的乳牛大脑中动脉平滑肌细胞上观察药物的作用.结果谷氨酸(10～200μmol·L-1)不能增加或减少细胞胞浆静息游离Ca2+浓度([Ca2+]i)和ATP触发的Ca2+内流(谷氨酸10～400μmol·     

Relationships between Ca2+ uptake by a microsomal fraction of guinea-pig taenia caecum and its relaxation

A microsomal fraction isolated from guinea-pig taenia caecum can accumulate calcium ions in the presence of ATP and MgCl₂. This calcium-accumulating ability depends on the ATP concentration in the reaction mixture, and its pH optimum is near 7·8. Procaine and quinidine inhibit Ca²⁺ accumulation by fraction and suppress the relaxation of this tissue induced by papaverine, isoprenaline and phenylephrine. These results suggest that Ca²⁺ accumulation by the microsomal fraction isolated from guinea-pig taenia caecum plays an important role during the relaxation of this smooth muscle. Cyclic adenosine 3′,5′-monophosphate (cAMP) does not accelerate Ca²⁺ accumulation by the microsomal fraction. The failure of cAMP to accelerate Ca²⁺ uptake by this fraction implies that some unknown steps or factors may exist between the intracellular increment of cAMP and the following relaxation of taenia caecum.     

Effect of papaverine on cyclic nucleotide levels in the isolated rat aorta.

An increase in cAMP but no significant modification in cGMP content could be demonstrated in rat aorta strips after applying papaverine in concentrations which reduced contractile responses. Accumulation of cAMP was induced in noradrenaline-stimulated on K+-depolarized strips, under omission of external Ca2+. Thus the elevation of cAMP level preceded the reduction of contraction subsequently elicited by readdition of Ca2+. The effects could not be dissociated under the experimental conditions used here.     

羟苯氨酮激活家兔血管平滑肌细胞钙敏感钾通道

目的研究羟苯氨酮(oxyphenamone,Oxy)扩张血管作用机理。方法用全细胞膜片钳技术,监测家兔肠系膜阻力血管平滑肌细胞钙敏感钾通道电流变化以及Oxy对其的影响。结果0.1 μmol·L^-1 Oxy明显增加钙敏感钾通道电流,冲洗后恢复至给药前水平;0.01～10 μmol·L^-1 Oxy明显增加钙敏感钾通道电流,且呈现浓度依赖性。结论 Oxy呈浓度依赖性和可逆性的增大血管平滑肌细胞钙敏感钾通道电流。     

环维黄杨星D对分离大鼠心室肌细胞内Ca2+和L型钙电流的影响

目的研究环维黄杨星D（CD）对大鼠心室肌细胞内Ca²⁺动员和L型钙电流(I_{Ca-L/sub>)的影响。方法采用全细胞膜片钳和激光扫描共聚焦显微术研究CD对心肌细胞ICa-L/sub>以及氯化钾、咖啡因诱发心肌细胞内Ca²⁺动员的影响。结果CD浓度依赖性抑制ICa-L/sub>。指令电压为10 mV时，1和10 μmol·L^-1 CD分别使ICa-L/sub>电流密度从（-9.9±1.8）pA/pF降至（-6.4±1.4）pA/pF和（-4.2±0.6）pA/pF。共聚焦实验显示1和10 μmol·L^-1 CD不影响静息心肌细胞［Ca²⁺］i?/sub>，对氯化钾诱发［Ca²⁺］i?/sub>升高水平无明显抑制作用；咖啡因引起的细胞内Ca²⁺动员可被CD进一步增强。结论CD浓度依赖性抑制大鼠心室肌细胞ICa-L/sub>，并有促进咖啡因诱发心肌细胞内Ca²⁺释放的作用。}     

某些因素对菠萝中菠萝蛋白酶热稳定性的影响

当温度恒定时A,菠萝中菠萝蛋白酶的热失活过程遵循一级蜕变规律d[E]/dt=-Kd.t,失活半寿期是常数,可以用作衡量菠萝蛋白酶热稳定性的指标.某些羧酸盐和金属离子能明显延长菠萝蛋白酶在较高温度下的半寿期.这些物质的稳定化作用可能是由于它们影响了溶剂结构和疏水相互作用,从而维护了酶分子的活性三维构象的结果.     

巯亚硝基卡托普利对环匹阿尼酸引起的平滑肌细胞胞浆游离Ca2+浓度升高作用的影响

目的探讨巯亚硝基卡托普利(S-nitrosocaptopril,CapNO)对Ca 2+池操纵性Ca2+内流信号转导过程的影响.方法以Fura-2 荧光探针测定胞浆游离Ca2+ 浓度([Ca2+]i ).结果①CapNO(20～120 μmol·L -1)呈浓度依赖性抑制环匹阿尼酸(cyclopiazonic acid, CPA)引起的 [Ca2+]i升高,80 μmol·L-1 CapNO为最大效应浓度.相同浓度的captopril对CPA升高[Ca2+ ]i无明显抑制作用.②在80 μmol·L-1 CapNO抑制CPA引起[Ca2+]i升高作用的基础上(31%±11%);随后加入1 μmol·L-1硝苯地平不能降低[Ca2+ ]i,再加入20 μmol·L-1SK&F96365(最大效应浓度)可进一步降低 [Ca 2+]i(54%±18%),其中SK&F96365净抑制率为24%±10%,与SK&F96365单独作用抑制率(54%±11%)比较差异有显著性.③不同顺序给予最大效应浓度CapNO(80 μmol·L -1)和tyrphostinAG490(2 μmol·     

Effects of papaverine on isolated rabbit papillary muscle

The effect of papaverine on the positive inotropic response to isoprenaline and to calcium was studied on the rabbit isolated papillary muscle; theophylline and the calcium antagonistic D600 were used for comparison. The dose—response curve for isoprenaline was shifted to the left by papaverine (3 × 10⁻⁶ to 3 × 10⁻⁵ M), in a dose-dependent manner, while that for calcium was not affected by the same concentration. In this respect papaverine was about 30 times more potent than theophylline. In the presence of papaverine isoprenaline induced arrhythmic contractions of the papillary muscle: the incidence of arrhythmic contractions correlated to the concentration of papaverine. Papaverine 10⁻⁵ to 10⁻⁴ M caused only a positive inotropic response whereas 3 × ⁻¹⁰ to 10⁻³ M induced a biphasic response, i.e., after a positive inotropic effect followed a negative one. In the presence of 3 × 10⁻⁴ M papaverine isoprenaline failed to cause a positive inotropic response but exclusively induced arrhythmic contractions. Calcium, on the other hand, readily antagonized the negative inotropic effectof papaverine (3 × 10⁻⁴ M) and caused a contracture of the papillary muscle. The results indicate that papaverine (3 × 10⁻⁶ to 10⁻⁵ M) like theophylline (10⁻⁴ to 10⁻³ M) produces its effect by phosphodiesterase inhibition and thereby specifically potentiates the response through β-adrenoceptor stimulation. In higher concentrations (3 × 10⁻⁴ to 10⁻³ M) it act as a calcium antagonistic, like D600, and furthermore may interact with calcium moving through myocardial cell membranes to cause a contracture via a mechanism which it shares with theophylline.     

吡喹酮对日本血吸虫雄虫的Ca2+,Mg2+,K+与Na+的含量及45Ca2+在虫体内分布的影响

日本血吸虫雄虫在4℃或37℃的HBS及无⁴⁵Ca²⁺的HBS中经吡喹酮1或30μg/ml作用0.5～2h后,未见虫的Ca²⁺,Mg²⁺含量有明显变化,但除4℃的HBS组外,余2组虫的K⁺含量明显减少,而虫的Na⁺含量的增加则不明显。在含30 mM Mg²⁺的HBS中,雄虫经吡喹酮作用1h后,虫的Mg²⁺含量明显增加。在37℃的HBS中,血吸虫雄虫经吡喹酮1μg/ml作用5～60min后,虫的皮层胞质中的⁴⁵²⁺含量的百分比较各相应对照组的明显减少,而虫体肌肉的则相反。在4℃的HBS或无⁴⁵Ca²⁺的HBS中,吡喹酮对⁴⁵²⁺在虫体内的分布无明显影响。     

缬沙坦和苯那普利对自发性高血压大鼠心肌钠泵和钙泵的影响

目的 比较缬沙坦和苯那普利对自发性高血压大鼠(SHR)心肌Na+-K+- ATP酶和Ca2+- ATP酶活性的影响.方法将24只雄性14周龄SHR分为生理盐水组、苯那普利 1 mg·kg     

Action of angiotensin II on teh electrical and mechanical activity of rat uterin smooth muscle

The effect of angiotensin II (A II) were studied on membrane potentials, ionic currents and isometric contractions in uterine smooth muscle strips from pregnant rats. In reference solution, A II in a low concentration (5 × 10^?9 M) exerted no effect on the resting potential or the action potential amplitude by significantly increased the rate of repetitive firing. However, in tetraethylammonium chloride (TEA)-containing solution, an increased in the action potential amplitude was always observed. The inward and outward currents were increased simultaneously, so that it was necessary to block the outward current with TEA ions in order to measure the enhancement of the inward current. The reduction of the deactivation time constants of the outward current as well as the increase in the inward current intensity could account for the acceleration of rhythmich activity in the presence of the peptide. The mechanical response to A II consisted of early tetanus which was followed by increased twitch contractions. The calcium contractures were also increased in depolarized strips. The tetanus could be dependent on the increase in and prolongation of repetitive firing while the enhancement of twitch contractions and calcium contractures could be explained by the increase in inward current intensity.     

The effect of staphylococcal alpha toxin on the superprecipitation and Ca2+-uptake of isolated arterial smooth muscle preparations

The effects of Staphylococcal alpha toxin from culture filtrates of Staphylococcus aureus, strain Wood 46, on superprecipitation of actomyosin and Ca²⁺-uptake of microsomes and fragments of plasma membrane from bovine carotid arteries were followed. It was found that alpha toxin inhibits the active Ca²⁺-uptake by smooth muscle microsomes and fragments of plasma membrane and liberates bound calcium. The toxin causes in the absence of free Ca²⁺ superprecipitation of actomyosin and activation of ATP-ase. The liberation of calcium from cellular structures and the inhibition of Ca²⁺ transport into these structures by alpha toxin could be responsible for its spasmogenic action.     

氯通道阻断剂对α1-肾上腺素受体亚型引起的Ca2+内流的影响

目的探讨氯通道阻断剂在α     

Effect of doxorubicin and rubidazone on respiratory function and Ca2+ transport in rat heart mitochondria

The effect of 2 cardiotoxic anthracycline antibiotics on rat heart mitochondria was investigated in vitro and in vivo. Doxorubicin (D) caused marked inhibition of electron transfer reactions and of Ca²⁺ uptake into mitochondria when Ca²⁺ translocation was energized by electron transfer activities. In vitro rubidazone (R) was a potent uncoupler of oxidative phosphorylation. It inhibited Ca²⁺ translocation energized by both electron transfer activities and ATP splitting. In vivo R also caused marked uncoupling of oxidative phosphorylation, but had only a weak and transient effect on Ca²⁺ uptake when energy was provided by electron transfer activities.     

Relaxant effect induced by wogonin from Scutellaria baicalensis on rat isolated uterine smooth muscle

Context: Wogonin is a flavone derivative isolated from Scutellaria baicalensis Georgi (Labiatae) root, which is a traditional Chinese drug used as an anti-inflammatory and for management of dysmenorrhea.

Objective: The effect of wogonin on the uterus has not yet been examined. We investigated the relaxant effects of wogonin on contractile activity of isolated uterine strips of rats.

Materials and methods: The effect of wogonin on spontaneous uterine contraction, and uterine contraction induced by agonists, K⁺-depolarization and oxytocin in Ca²⁺-free solution was observed. To clarify the type of potassium channel, we tested the effects of 4-aminopyridine, tetraethylammonium and glibenclamide.

Results: Wogonin reduced the contractile amplitude of uterine strip smooth muscle of rats in a dose-dependent manner. The concentration of wogonin for reducing the contraction amplitude by 50% (IC₅₀) on spontaneous contractions was 60.5 μM. Wogonin also inhibited the contraction induced by three agonists (oxytocin, prostaglandin F_2α and acetylcholine). For the uterine strips pretreated with oxytocin in Ca²⁺-free solution or K⁺-depolarization, wogonin showed relaxant effect on the induced uterine contractions. In addition, whereas the inhibitive effect of wogonin on the contraction of uterine smooth muscle in rats could be partly blocked by 4-aminopyridine and tetraethylammonium, it was not influenced by glibenclamide.

Discussion and conclusion: Wogonin significantly inhibited the contraction of rat uterine smooth muscle probably through the inhibition of the inflow of extracellular calcium into cells via cell membrane, and intracellular release of calcium ions. In addition, the relaxant effect induced by wogonin might be due in part to the opening of voltage-dependent and large conductance Ca²⁺-activated K⁺ channels.     

Immunohistochemical and functional studies on calcium-sensing receptors in rat uterine smooth muscle

1. Activation of calcium‐sensing receptors (CaS) leads to relaxation of vascular smooth muscle. However, the role of CaS in uterine smooth muscle is unknown. Therefore the aim of the present study was to investigate the expression and function of CaS in the uterus. 2. The expression of CaS in the oestrogen‐dominated rat uterus was investigated using immunohistochemistry. The effects of putative CaS ligands on oxytocin‐induced contractions of longitudinally orientated uterine strips from oestrogen‐dominated rats were determined at reduced extracellular Ca²⁺concentrations using conventional organ bath techniques. 3. Immunohistochemical evidence showed the presence of CaS in the endometrium and smooth muscle layers of the rat uterus. Oxytocin‐induced contractions were inhibited by cations (Gd³⁺ > Ca²⁺ = Mg²⁺), polyamines (spermine > spermidine) and the positive allosteric modulators cinacalcet and calindol. However (R)‐ and (S)‐cinacalcet were equipotent, indicating a lack of stereoselectivity, and the negative allosteric modulator calhex‐231 also caused dose‐dependent relaxation. In addition, although intermediate‐conductance calcium‐activated potassium channels and cytochrome P450‐dependent signal transduction have been implicated in CaS‐induced relaxation of vascular smooth muscle, neither Tram‐34 nor miconazole (1 μmol/L), which block these pathways, respectively, had any effect on the ability of cinacalcet to inhibit oxytocin‐induced contractions. 4. Calcium‐sensing receptors are expressed in smooth muscle layers of the rat uterus and their ligands produce potent relaxation of longitudinally orientated uterine strips. However, the pharmacological profile of inhibition of contractility by CaS ligands is not consistent with a role for CaS in the regulation of uterine contractility in the rat.