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1.
The effects of the water extract of Sinomeni Caulis et Rhizoma (SCR-WE) and its major constituents, sinomenine (SIN) and magnoflorine (MAG), on moderate hemolysis induced by lysophosphatidylcholine (LPC) were investigated in rat erythrocytes and compared with the anti-hemolytic effects of lidocaine (LID) and propranolol (PRO) as reference drugs. LPC caused hemolysis at concentrations above the critical micelle concentration (CMC), and the concentration of LPC producing moderate hemolysis (60 %) was approximately 10 μM. SCR-WE at 1 ng/mL–100 μg/mL significantly inhibited the hemolysis induced by LPC. SIN and MAG attenuated LPC-induced hemolysis in a concentration-dependent manner from very low to high concentrations (1 nM–100 μM and 10 nM–100 μM, respectively). In contrast, the inhibiting effects of LID and PRO on LPC-induced hemolysis were observed at higher concentrations (1–100 μM) but not at lower concentrations (1–100 nM). Neither SIN nor MAG affected micelle formation of LPC, nor, at concentrations of 1 nM–1 μM, did they attenuate the hemolysis induced by osmotic imbalance (hypotonic hemolysis). Similarly, SCR-WE also did not modify micelle formation or hypotonic hemolysis, except at the highest concentration. These results suggest that SIN and MAG potently protect the erythrocyte membrane from LPC-induced damage and contribute to the beneficial action of SCR-WE. The protective effects of SIN and MAG are mediated by some mechanism other than prevention of micelle formation or protection of the erythrocyte membrane against osmotic imbalance. 相似文献
2.
We examined the effects of the angiotensin converting enzyme (ACE) inhibitors captopril, enalaprilat, quinapril, and trandolapril, and their active metabolites quinaprilat and trandolaprilat, on hemolysis induced by lysophosphatidylcholine (LPC) in human erythrocytes. LPC induced hemolysis at the concentrations above the critical micelle concentration (4 microM). Propranolol, used as a reference drug, attenuated the 50% hemolysis induced by 6 microM LPC at concentrations ranging from 100 nM to 100 microM. Similarly, quinaprilat (10 microM) and trandolaprilat (10, 100 microM) significantly attenuated the LPC-induced hemolysis, but other ACE inhibitors did not. Since propranolol possesses a membrane stabilizing action correlated with high lipophilicity, it appears that the high lipophilicity of quinaprilat or trandolaprilat is responsible for the protection from the damage induced by LPC. However, quinapril and trandolapril were not effective, although both drugs have higher lipophilicity than quinaprilat and trandolaprilat. Hence, it is suggested that the high lipophilicity alone may not contribute to the protective effects of ACE inhibitors against LPC-induced hemolysis. None of ACE inhibitors attenuated the hypotonic hemolysis (60 mM NaCl), although propranolol did. Furthermore, neither propranolol (100 microM) nor quinaprilat (50 microM) and trandolaprilat (50 microM) affected LPC micelle formation, suggesting that these drugs do not directly bind to LPC. We therefore believe that the protective effects of quinaprilat and trandolaprilat on the LPC-induced hemolysis may be related physicochemically to their highly lipophilic and ACE inhibitory structures, which probably maintain erythrocyte membrane integrity by a mechanism other than ACE inhibition, prevention of LPC micelle formation or protection against osmotic imbalance. 相似文献
3.
The interactions of ahomologue series of surface-active alky Itrimethylammonium salts (C 10-C 20) with the rat erythrocyte membrane were studied. The surfactants were found to have a biphasic effect on the erythrocyte membrane. At low concentrations they protected or stabilized erythrocytes against hypotonic haemolysis, but at higher concentrations they caused rapid haemolysis. The stabilizing and lytic effect increased with an increase in length of the alkyl chain to maximum activity at about C 16. It is suggested that laminar-micellar transitions in the lipid bilayer of the membrane are responsible for the lytic activity of the surfactants. Micellar regions in the lipid bilayer abolish the ability of the membrane to prevent the free exchange of ions, and haemolysis of the cell results from a secondary osmotic effect. The stabilizing effect, on the other hand, is proposed to stem from an expansion of the membrane caused by a fluidizing effect of the surfactants on the lipid bilayer. Binding studies with the C 16 homologue revealed that at a concentration causing 50 per cent haemolysis in an isotonic solution there are about 780,000 molecules bound per μm 2 of the erythrocyte membrane. At a concentration giving 50 per cent protection against hypotonic haemolysis, the number of molecules bound per μm 2 of the erythrocyte membrane was estimated to be 190,000. 相似文献
4.
The influence of the antivirus drugs amantadine and rimantadine and of the anionic analogue 1-adamantane-carboxylic acid on a range of properties of human erythrocyte membrane and of thrombocytes has been compared with the effect of the local anaesthetic tetracaine. At low antiviral drug concentrations the abilities of the drugs to induce erythrocyte shape change and suppress osmotic haemolysis were quantitatively proportional to their clinical potency (rimantadine more effective than amantadine at the same concentration). Rimantadine was also more effective than amantadine in suppressing influenza virus-erythrocyte fusion and viral induced haemolysis. The antiviral drug effects were qualitatively similar to those induced by tetracaine. At the quantitative level, tetracaine was more efficient than the antiviral drugs in inhibiting osmotic haemolysis, virus membrane fusion and platelet aggregation. In the absence of any specificity of the antiviral drug effects we argue for a lysosomotropic mode of drug action, i.e. that the drugs modify virus-membrane interactions by changing the endosomal or lysosomal pH. 相似文献
5.
Abstract— Furanocoumarin 8-methoxypsoralen (8-MOP) (1–100 μg mL ?1) in the dark showed a protective affect against hypotonic haemolysis of the erythrocyte membrane. However, the effect against heat-induced haemolysis was dependent on the concentration of 8-MOP; lower concentrations of 8-MOP showed an inhibiting effect, whereas higher concentrations caused acceleration of haemolysis. 8-MOP was not able to induce haemolysis in isotonic solution at 20 or 37 C. Reaction of erythrocytes with 8-MOP in the dark resulted in a shrinkage of the cells and alterations of their shapes. We conclude that modification of erythrocyte membrane by 8-MOP proceeds via reaction with membrane lipids and proteins. This indicates that the effect on the cell membrane plays an important role in the mechanism of the action of 8-MOP on the cells. 相似文献
6.
The present study was undertaken in order to examine whether dilazep (1,4-bis-[3-(3,4,5-trimethoxybenzoyloxy)propyl]perhydro-1, 4-diazepine dihydrochloride monohydrate) attenuates myocardial acidosis induced by coronary artery occlusion in dogs. In dogs with nonischemic normal heart, dilazep (300 or 500 micrograms/kg i.v.) increased blood flow in the left anterior descending coronary artery (LAD) with a decrease in heart rate and diastolic blood pressure. In other dogs, LAD flow was reduced by an occluder by 57 to 68% (partial occlusion) for 90 min. Partial occlusion for 30 min decreased myocardial pH by 0.67 to 0.87 pH units, increased ST segment of the surface electrocardiogram, and decreased regional myocardial contractile force. Dilazep was injected i.v. 30 min after partial occlusion. The decrease in myocardial pH induced by partial occlusion was attenuated by the injection of 300 micrograms/kg of dilazep insignificantly and by that of 500 micrograms/kg of dilazep significantly. Restoration of myocardial [H+] induced by dilazep was calculated from the myocardial pH data. Dilazep (500 micrograms/kg) restored myocardial [H+] induced by partial occlusion by 56.7%, and saline solution restored it by 27.4% 60 min after the drug injection, the actual restoration induced by dilazep being 29.3%. Dilazep, however, did not restore the ST segment elevation and contractile force decrease. It is concluded that dilazep attenuates myocardial acidosis during ischemia. 相似文献
7.
The effects, at pH 7.0, of a series of 0.2 mM phosphatidylcholines (PC), namely dicaproyl-PC (DCPC), didecanoyl-PC (DDPC), dilauroyl-PC (DLaPC), dimyristoyl-PC (DMPC), dipalmitoyl-PC (DPPC), dioleoyl-PC (DOPC) and dilinoleoyl-PC (DLPC) and a series of 0.2 mM fatty acid salts (namely sodium myristate, palmitate, stearate, oleate and linoleate) upon the erythrocyte haemolysis induced by 2 mM sodium taurodeoxycholate (STDC) were determined. The influence of egg PC and dihexadecyl phosphate (DHDP) concentration upon the haemolysis induced by 1.4 mM sodium deoxycholate (SDC), 2 mM STDC and 0.1 mM lysophosphatidylcholine (LPC) were also established. A bile salt:egg PC mole ratio of 0.5 virtually abolished the haemolysis induced by SDC and STDC, whereas the same ratio of LPC:egg PC only reduced haemolysis from 65 to 40% (maximum haemolysis). DHDP had no effect on the haemolytic action of SDC or STDC. The salts of the fatty acids were non-haemolytic, and when mixed with STDC did not affect the level of haemolysis induced by the bile salt. In contrast, DDPC and DLaPC enhanced the haemolysis of STDC and DCPC had no effect, whereas DMPC, DPPC, DSPC, DOPC, DLPC and egg PC all reduced haemolysis. Maximum reduction was determined for DMPC and egg PC. The mixed micelle preparation temperature (either room or 60 degrees C) and temperature of incubation (either 20 degrees C for 30 min or 37 degrees C for 5 min) had only minor effects on the net haemolysis induced by STDC. These findings may be of significance in understanding the aetiology of certain gastrointestinal diseases and in determining whether mixed bile salt micelles have a role as drug penetration enhancers. 相似文献
8.
In this study, we continued our investigations concerning the interaction of Uncaria tomentosa extracts with the human erythrocytes. The analysis of the size and shape of the erythrocytes by means of flow cytometry and phase contrast microscopy was performed. We executed our experiments using ethanolic and aqueous extracts from the leaves and bark of U. tomentosa. Disturbances were observed in the size and shape of the erythrocytes incubated with ethanolic and aqueous extracts at the concentrations of 100 μg/mL and 250 μg/mL, respectively. The observed changes were probably related to the entry of polyphenolic compounds contained in U. tomentosa extracts into erythrocyte membrane. Externalization of phosphatidylserine on the erythrocytic surfaces was also noticed during incubation with extracts at concentration of 250 μg/mL. We concluded that all of the extracts examined induced changes in the erythrocyte membrane properties, whereas ethanolic extracts from bark induced the most significant changes. The possible binding of polyphenols to the erythrocyte surface may have accounted for the protective properties of extracts against haemolysis of RBCs, which was observed in our previous study (Bors et al., 2011), but considerable incorporation of polyphenols into cell membranes can result in disturbance of phosphatidylserine transport and changes in erythrocyte shape. Nevertheless the results of the investigations showed that considerable morphological changes appear only as a result of erythrocyte exposure to high concentrations (50 ppm and 100 ppm) of the extracts studied, thus they should not lead to clinical erythrocytic damage if recommended doses of U. tomentosa preparations are administrated. 相似文献
9.
The aim of the present study was performed to determine whether a novel histone deacetylase (HDAC) inhibitor, N-(2-aminophenyl)-4-{[benzyl(2-hydroxyethyl)amino]methyl} benzamide (K-183), prevents a reversible cardiac hypertrophy induced by isoproterenol and improves left ventricular (LV) dysfunction in rats. Either isoproterenol or vehicle was infused for 3 days by osmotic minipump. One hour prior to the implantation of isoproterenol, K-183 or trichostatin A (TSA) was injected twice a day for 3 days. We recorded continuous LV pressure-volume (P-V) loops of in situ hearts one hour after removal of the osmotic minipump. LV work capability (systolic P-V area at midrange LV volume: PVA(mLVV)) and hemodynamics were evaluated. K-183 per se induced neither cardiac hypertrophy nor collagen production. Although K-183 did not prevent the hypertrophy, where PVA(mLVV) remained decreased, K-183, differently from TSA, significantly attenuated the decrease of cardiac output and the increase of effective arterial elastance in the hypertrophied heart. These results indicate that the novel HDAC inhibitor K-183 has some beneficial effects on hemodynamics, although K-183 has no effects of anti-hypertrophic modalities. 相似文献
10.
The haemolytic effect of verapamil on red blood cells (RBCs) exposed to varying osmolarity was investigated. The experimental approach used a modified red cell haemolysis assay with concentrations of verapamil ranging from 50-1500 microM compared to drug free controls. The time-course of haemolytic effects was also investigated. We also briefly determined the haemolytic effects of verapamil in Ca2+-free conditions (with added EGTA). In conditions representing decreasing osmolarity (dilution from 140-0 mM NaCl) there was a significant increase in erythrocyte haemolysis that was also dependent on verapamil concentration (ANOVA, p<0.05). The red cells also showed a significantly increased rate of haemolysis over 5 h with increasing verapamil concentration (ANOVA, p<0.05). The degree of RBC hypotonic haemolysis was significantly increased in a Ca2+-free medium (+EGTA) compared to normal saline and this effect was exacerbated by additions of verapamil (ANOVA, p<0.05). Overall the data suggested that verapamil can cause haemolysis of RBCs in a predictable time- and concentration-dependent manner, and that verapamil increases the fragility of the erythrocytes further during hypotonic osmotic stress and Ca2+-free conditions. The mechanism of verapamil-dependent haemolysis could be directly related to the observed biphasic concentration-effect and could consequently involve several ion transport pathways. 相似文献
11.
We studied the interaction of double-chained cationic surfactants, dimethyldialkylammoniums, (CH3)2N+(CnH2n+1)2, with the lipid bilayer of guinea-pig erythrocytes by observing the haemolysis, aggregation and shape change in the erythrocytes. In the presence of sonicated dispersions of the five dimethyldialkylammoniums tested (n = 10, 12, 14, 16 and 18), haemolysis was induced dose dependently, and at 0.1 mM or higher concentrations, haemolysis was induced more rapidly by dimethyldialkylammoniums with shorter alkyl chains. The cationic surfactants with longer alkyl chains, such as dimethyldipalmitylammonium, induced aggregation of the erythrocytes before haemolysis fully progressed. The vesicles of these long-chain dimethyldialkylammoniums in the presence of phosphatidylcholines with unsaturated fatty acyl chains markedly reduced the haemolysis rates. Furthermore, in the presence of phosphatidylcholines with unsaturated acyl chains the formation of tightly aggregated structures of several erythrocytes was observed. These findings, and analysis by spin label 5-doxylstearic acid, indicate that phosphatidylcholines enriched with unsaturated acyl chains stabilize the cationic vesicles of long-chain dimethyldialkylammoniums and the interaction with the lipid bilayer of erythrocyte membranes as cationic vesicles became prominent. 相似文献
12.
1 The interaction of nitric oxide and ATP in the non‐adrenergic, non‐cholinergic (NANC) motor responses and the presence of NADPH‐diaphorase and quinacrine‐positive myenteric neurones were studied on guinea‐pig ileum using mechanographic, histochemical and quinacrine‐fluorescence techniques. In the presence of phentolamine, propranolol and atropine, the non‐precontracted longitudinally oriented organ bath preparations responded to sodium nitroprusside (1–100 μm ) or ATP (5–50 μm ) with tetrodotoxin (0.1 μm )‐resistant relaxation or contraction, respectively. The effects of ATP were suramin (50 μm )‐ and apamin (5 μm )‐sensitive. 2 The NANC motor responses elicited by electrical stimulation (0.8 ms, 1–20 Hz, 20 s) consisted of tetrodotoxin‐sensitive relaxation phase followed by a phase of twitch‐like and tonic contractions. 3 NG‐nitro‐L‐arginine (L‐NNA, 0.1–0.5 mm ) inhibited or abolished the relaxation phase. L‐arginine (0.5 mm ), but not D‐arginine (0.5 mm ), restored the relaxation phase in L‐NNA‐pretreated preparations. The relaxation phase increased after ATP‐induced desensitization of purinoceptors and in the presence of suramin (50 μm ) but was abolished by apamin (5 μm ). 4 The phase of contractions was enhanced by L‐NNA (0.1–0.5 mm ) and restored by L‐arginine (0.5 mm ). The twitch‐like and tonic contractions were decreased during ATP‐induced purinoceptor desensitization and in the presence of suramin (50 μm ). Apamin (5 μm ) inhibited the tonic contractions. 5 The desensitization of purinoceptors by ATP did not change the L‐NNA‐induced inhibition of the relaxation phase but decreased the L‐NNA‐increased phase of contractions. L‐NNA reduced the relaxation phase and increased the phase of contractions during purinoceptor desensitization. 6 We conclude that in the longitudinal muscle layer of the guinea‐pig ileum, nitric oxide mediates the relaxation phase while ATP contributes via smooth muscle P2 purinoceptors to the phase of contractions suggesting a postjunctional functional antagonism between nitric oxide and ATP. The presence of NADPH‐diaphorase‐ and quinacrine‐positive neuronal cells and processes running to the muscle cells confirms a physiological role of nitric oxide and ATP in the ileal neurotransmission. 相似文献
13.
The time-course of haemolysis induced by alkyltrimethylammonium bromides, alkyl sulphates, octaethyleneglycol alkyl ethers, and ZWITTERGENT detergents (C10-C16) was studied. A considerable lag in the development of haemolysis was observed for the C10 and C12 derivatives. The lag exceeded 30 min at low or moderate concentrations of the surfactants. Most of the C14 and C16 derivatives showed no lag but the time-course of the haemolytic reaction of these derivatives indicated biphasic kinetics of haemolysis. With those surfactants showing a lag the critical micelle concentration (cmc) of the surfactants was above the concentrations used in the experiments, whereas cmc in the case of those surfactants showing no lag was close to or slightly below. It is concluded that the differences in the time-course of the haemolytic reaction shown by different derivatives are not connected with the occurrence of micelles in the bulk solution, but that the differences in time-course of the haemolytic reaction reflect differences in the rate of those changes in the membrane molecular organization which precede haemolysis. 相似文献
14.
目的 研究异丙酚对离体大鼠海马神经元缺氧损伤的保护作用及其机制。方法 以原代培养的大鼠海马神经元作为研究对象 ,建立缺氧、H2 O2 和谷氨酸损伤模型 ,用MTT法测定神经元存活率。采用激光扫描共聚焦显微镜动态监测缺氧前后 ,单个海马神经元内Ca2 + 浓度和线粒体膜电位 (△Ψm)的变化。用电子自旋共振技术测定异丙酚对羟基自由基和超氧阴离子自由基的清除作用。结果 6~ 4 8mg·L-1浓度的异丙酚可明显降低神经元缺氧损伤时的细胞死亡率 (P <0 0 1) ,作用程度均呈剂量相关 (r =0 89,P <0 0 5 ) ;2 4~ 4 8mg·L-1浓度的异丙酚可明显降低H2 O2 损伤时的细胞死亡率 (P <0 0 1) ;12~ 4 8mg·L-1浓度的异丙酚可明显降低谷氨酸损伤时的细胞死亡率 (P <0 0 1)。 3~ 4 8mg·L-1异丙酚对缺氧诱发的细胞内钙离子超载有抑制作用(P <0 0 5 ) ;12、4 8mg·L-1异丙酚能减缓缺氧引起的△Ψm降低 (P <0 0 1)。 12、4 8mg·L-1异丙酚对羟基自由基的清除率分别为 17 1%和 2 1 1% ,但对超氧阴离子自由基无清除作用。结论 异丙酚对离体培养的大鼠海马神经元缺氧性损伤具有保护作用 ,其作用机制部分与异丙酚抑制缺氧引起的 [Ca2 + ]i 异常升高、抑制线粒体膜电位的下降和清除羟基自由基有关 相似文献
15.
Concentrations of dilazep which were ineffective in altering the muscular tone of the guinea-pig taenia caeci (0.03, 0.3 microM) or the phasic mechanical activity of the rabbit proximal ileum (0.03 microM) markedly potentiated the inhibitory action of adenosine on both these parameters. Dilazep, 0.3 microM or greater, dose-dependently inhibited the mechanical activity of the proximal ileum. This inhibitory action was probably mediated by more than one mechanism, as shown by the fact that theophylline (50, 100 microM) antagonized the effect at lower dilazep concentrations (up to 3 microM) leaving essentially unchanged the response to higher concentrations (6, 10 microM). Similarly, the responses to low doses of dilazep were reduced after desensitization of the organ to adenosine, whilst the responses to higher doses were unaffected by this procedure. In a Ca2+-free, high-K+ medium, dilazep (1-10 microM) caused a parallel shift to the right of the Ca2+-induced contractions of the guinea-pig taenia caeci. Adenosine showed only slight Ca2+-antagonistic properties within the mM range of concentrations. These findings suggest that, at the higher concentration tested, dilazep exhibits Ca2+-antagonistic properties unrelated to its adenosine-mediated mode of action. 相似文献
16.
Original tablets of Cormelian [= 50 mg 1,4-bis[3-(3,4,5-trimethoxybenzoyl-oxy)-propyl]-perhydro-1,4-diazepine (dilazep)] and Cormelian-Digotab (= 50 mg dilazep + 0.2 mg beta-acetyl-digoxin) were produced with 3H-dilazep as prescribed in the special galenic technique. After application of a single oral dose of two tablets dilazep to 9 patients serum concentration was analysed at different times up to 24 h p.a.; the renal excretion rate of dilazep and metabolites was determined up to 48 h. Two tablets of the combination were given to 4 of these patients 4 days after application of dilazep and the corresponding analysis were repeated; in the serum of these patients the concentration of glycoside was determined by radioimmuno assay. The following results were obtained. 1. Differences in serum concentrations and renal excretion rates of dilazep and metabolites were not observed after application of the mono- and combination product. In comparison to results after oral application of pure dilazep in gelatin capsules the serum concentrations 1 h after application of Cormelian and Cormelian-Digotab were statistically significantly higher. With reference to comparable total absorption rates these results may be representative for a possibly retarded absorption rate of dilazep given as pure substance. An influence of the different galenic techniques on the intensity and direction of metabolites could not be substantiated. 2. By large dispersions of the single values high absolute and relative concentrations of beta-acetyl-digoxin were found in the serum of all the 4 patients after application of combination. Contrary to two commercial products, applied to each of 10 test persons under comparable conditions, statistically higher serum concentrations of glycoside were analysed 1 h after application of the combination. The results of these studies confirm a positive influence of the galenics on the biological availability of both the components in the combination drug Cormelian-Digotab. 相似文献
17.
Effect of 3-4-dihydro-8-(2-hydroxy-3-isopropylaminopropoxy)-3-nitroxy-2H-1-b enzopyran (K-351) infused into the renal artery on renin release during graded renal nerve stimulation (RNS) was investigated in pentobarbital-anesthetized dogs. K-351 (20 micrograms/min) produced significant suppression of the RNS-induced renin release; the renin secretion responses to RNS at lower frequencies (0.5 and 1 Hz) were almost abolished, and those at the highest frequency (3 Hz) were attenuated. K-351 also suppressed an increase in renal vascular resistance during RNS at 3 Hz. The same extent of inhibition in the renin secretion response to RNS was also obtained during infusion of DL-propranolol (100 micrograms/min). Inhibitory effect of K-351, prazosin, or phentolamine on the renal vasoconstriction induced by RNS and norepinephrine (NE) injected into the renal artery, an approximately 50% reduction in renal blood flow, was also assessed. K-351 and prazosin exerted a greater inhibitory effect on RNS-than on NE-induced vasoconstriction, and the opposite was true of phentolamine. The potency of K-351 in reducing the vasoconstriction due to RNS or NE was roughly estimated to be 10-30 times less than that of prazosin. These results suggest that K-351 shares beta- and alpha-adrenoceptor blocking properties, which effectively contribute to the suppression of adrenergically induced renin release and renal vasoconstriction. 相似文献
18.
Even though lacking mitochondria and nuclei erythrocytes do undergo apoptotic cell death which is characterized by breakdown of phosphatidylserine asymmetry (leading to annexin binding), membrane blebbing and cell shrinkage. Previously, we have shown that erythrocyte apoptosis is triggered by osmotic shrinkage at least in part through activation of cell volume-sensitive cation channels and subsequent Ca2+ entry. The channels could not only be activated by cell shrinkage but as well by replacement of Cl- with gluconate. Both, channel activity and annexin binding were sensitive to high concentrations of amiloride (1 mM). The present study has been performed to search for more effective blockers. To this end channel activity has been evaluated utilizing whole-cell patch-clamp and annexin binding determined by FACS analysis as an indicator of erythrocyte apoptosis. It is shown that either, increase of osmolarity or replacement of Cl- by gluconate triggers the activation of the cation channel which is inhibited by amiloride at 1 mM but not at 100 microM. Surprisingly, the cation channel was significantly more sensitive to the amiloride analogue ethylisopropylamiloride (EIPA, IC(50)=0.6+/-0.1 microM, n=5). Exposure of the cells to osmotic shock by addition of sucrose (850 mOsm) led to stimulation of annexin binding which was inhibited similarly by EIPA (IC(50)=0.2+/-0.2 microM, n=4). Moreover, annexin binding was inhibited by higher concentrations of HOE 642 (IC(50)=10+/-5 microM, n=5) and HOE 694 (IC(50)=12+/-6 microM, n=4). It is concluded that osmotic shock stimulates a cation channel which participates in the triggering of erythrocyte apoptosis. EIPA is an effective inhibitor of this cation channel and of channel mediated triggering of erythrocyte apoptosis. 相似文献
19.
目的观察比较染料木素(genistein,Gen)和17β-雌二醇(17β-estradiol,Est)对豚鼠乳头肌生理特性影响,研究Gen对豚鼠离体心肌的兴奋作用与肌质网Ca2+释放和摄取的关系。方法将乳头肌置于装有K-H液的灌流肌槽中,加入药物观察其生理特性及收缩活动的变化。结果Gen及17β-雌二醇浓度为1和10μmol·L-1均不影响肾上腺素诱发的心肌自律性,二者在50μmol·L-1时均能抑制自律性;Gen浓度为50μmol·L-1能降低心肌兴奋阈强度,Gen(1和10μmol·L-1)及17β-雌二醇(1~50μmol·L-1)不影响兴奋性阈强度;Gen(1~50μmol·L-1)不影响心肌功能不应期(FRP),17β-♂二醇(1~50μmol·L-1)延长心肌FRP;同时发现1~50μmol·L-1的17β-雌二醇抑制心肌的收缩活动,但同浓度的Gen可增强心肌的收缩活动。利罗丁(ryanodine)受体阻断剂钌红(10μmol·L-1)和利罗丁(1nmol·L-1)预处理可部分阻断Gen(50μmol·L-1)对心肌收缩的增强效应,利罗丁(20μmol·L-1)使Gen正性肌力作用完全阻断。肌质网钙泵阻断剂thapsigargin(1μmol·L-1)预处理也可部分抑制Gen(50μmol·L-1)对心肌收缩的兴奋作用。但特异性雌激素受体(ER)阻断剂ICI182,780(10μmol·L-1)和Na+-Ca2+逆交换抑制剂Kb-R7943(1μmol·L-1)预处理不影响Gen(50μmol·L-1)的正性肌力作用。结论Gen和17β-雌二醇均能降低心肌兴奋性和自律性,但Gen增强其收缩活动,而17β-雌二醇作用相反;Gen正性肌力作用与心肌细胞膜上的ER和Na+-Ca2+逆交换无关,可能与肌质网内Ca2+的释放和摄取有直接的关系。 相似文献
20.
Using a fluorescent Ca(2+)-sensitive dye, fura-2, and photometric fluorescence microscopy, we measured changes in cytosolic Ca2+ concentration ([Ca2+]i) in cultured human endothelial cells and studied the effect of dilazep on [Ca2+]i elevation induced by histamine. Histamine (1 microM) caused a rapid transient peak in the average [Ca2+]i of a group of cells (approximately 10(2) cells), followed by a decrease to a sustained elevation. Dilazep as well as diltiazem (1.0 to 100 microM) concentration-dependently inhibited the latter sustained elevation, which was eliminated by removal of extracellular Ca2+, while the initial transient response was not changed by dilazep at concentrations up to 100 microM. The IC50 values of dilazep and diltiazem were 16 and 58 microM, respectively. The patterns of the [Ca2+]i elevation responses to histamine were variable among individual cells. Some single cells showed a transient peak and a sustained elevation as observed in a group of cells. Some single cells caused a repetitive spikelike elevation of [Ca2+]i. Dilazep lowered the sustained elevation to the resting level and in some single cells, changed the sustained elevation to the spikelike elevation. The frequency of the spikelike [Ca2+]i elevation was also decreased by dilazep. Decrease in extracellular [Ca2+] showed the same pattern of inhibitory actions as dilazep did. These results indicate that dilazep inhibits the extracellular Ca2+ influx in endothelial cells. 相似文献
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