中国药理学报（英文版）杂志
Acta Pharmacologica Sinica
- 论文标题 期刊级别 审稿状态
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环磷酰胺对大鼠原肠胚前期末胚胎蛋白表达的影响
目的：确定原肠胚前期胚胎对发育毒性药物敏感的时间点，并建立评价Cyc诱导胚胎发育异常机制的分子生物学指标.方法：大鼠孕d 3 ip Cyc 10，20，40mg·kg-1，孕d 8 SDS-聚丙烯酰胺凝胶电泳定位大鼠胚胎蛋白.结果：Cyc 40mg·kg-1组70 kDa蛋白表达显著上调，14.4 kDa胚泡化特征性蛋白表达消失.结论：大鼠妊娠d 8为研究原肠胚前期胚胎发育毒性的较适时间点，孕d 8 70 kDa蛋白表达上调伴随14.4 kDa胚泡化特征性蛋白表达下调可作为该发育阶段胚胎毒性分子生物学评价指标。
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淀粉样β蛋白25-35诱导大鼠星形胶质细胞表达单胺氧化酶B
目的：观察淀粉样β蛋白25-35(Aβ 25-35)对大鼠星形胶质细胞内单胺氧化酶活性及表达的影响。方法：用免疫组织化学方法观察Aβ25-35对大鼠星形胶质细胞形态的影响；用荧光分光光度法检测MAO的活性；用RT-PCR观察A β25-35对MAO表达的影响。结果：Aβ25-35可诱导星形胶质细胞呈现激活形态，伴有胶质原纤维酸性蛋白染色增强。Aβ25-35可使星形胶质细胞内MAO-B活性增强，并呈剂量和时间依赖性。经RT-PCR检测发现，MAO-B活性增强是由于MAO-B mRNA表达升高所致。结论：Aβ25-35可选择性上调大鼠星形胶质细胞内MAO-B的表达，该作用在阿尔采末病的病理过程中可能具有重要意义。
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脊髓切片中运动神经元的膜片箝技术研究：一种分析药物作用的高效工具
AIM: To develop a tool for detailed analysis of spinally acting anesthetic and analgesic agents. METHODS:Studies were done on visually identified motor neurons in 400 μm thick spinal cord slices from 14- 23 d old rats using patch clamp techniques. Ethanol was used as a prototype general anesthetic agent. RESULTS: Cell bodies in the ventrolateral horn identified as motor neurons by retrograde fluorescent labeling had a mean dimension of 32 ±5μm (x±s, n = 25). Mean resting potential was - 62.8 ± 2.4 mV; input resistance was 44±24MΩ (n=19). Threshold was -44±7 mV,and action potential amplitude 101 ± 9 mV from baseline.Ethanol concentrations at and below 50-200 mmol/L decreased motor neuron excitability to the injected current; there was no effect on resting potential, but a variable reversible increase in input resistance. Ethanol reversibly depressed the excitatory postsynaptic potential,with a dose-response relationship similar to that previously observed for the population excitatory postsynaptic potential in intact spinal cord in vitro. Ethanol also reversibly depressed currents evoked by glutamate, reducing total charge transfer to 40％±26％ of control (x±s; n= 4). CONCLUSION: Reduction of connectivity in this relatively thick slice preparation does not significantly modify drag actions. The actions of ethanol on excitatory synaptic transmission observed in intact spinal cord are
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硝普盐、3-吗啉-悉尼酮亚胺和精胺对豚鼠胃窦环行肌钙敏感钾电流的影响
目的：探讨一氧化氮对豚鼠胃窦环行肌钙敏感钾电流的影响.方法：采用全细胞式的膜片箝方法，用精胺、硝普盐、3-吗啉-悉尼酮亚胺(SIN-1)作为一氧化氮供体.结果：外向钾电流被四乙铵(1 mmol·L-1)和ChTX(200 nmol·L-1)显著抑制.在穿孔膜式条件下，精胺(100μmol·L-1)、SIN-1(200 μmol·L-1)、硝普盐(100μmol·L-1)均增加钙敏感钾电流.1μmol·L-1亚甲蓝完全阻断硝普盐与SIN-1导致的增加效应.结论：一氧化氮增加豚鼠胃窦环行肌钙敏感钾电流，该效应可能通过环磷酸鸟苷介导.
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孤啡肽和阿片类配体与阿片孤儿受体相互作用的机制研究
研究孤啡肽和阿片类配体与阿片孤儿受体相互作用的分子机制。方法：用分子动力学方法计算孤啡肽的低能构象；通过分子对接程序将孤啡肽、阿片类配体对接到阿片孤儿受体的结合口袋中；通过结合能的计算研究配体对受体的亲和力与它们的结合能之间的关系。结果：孤啡肽(1-4)残基位于结合口袋的底部，孤啡肽(5-7)残基位于结合口袋的顶部，孤啡肽(8-17)残基与孤儿受体的第二膜外环区结合；阿片类配体和孤儿受体的结合方式与孤啡肽的情况类似，区别在于孤儿受体参与配体结合的残基种类和数量不同，因而亲和力不同；配体-受体的结合能与配体的亲和力之间有很好的相关性；预测了洛芬太尼四个异构体与阿片孤儿受体的亲和力。结论：该研究能够解释许多实验事实，有助于进一步理解阿片受体与配体相互作用的分子机制并设计新的分子生物学实验。
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人白介素16与HIV-1的CD4受体的相互作用
目的：研究人白介素-16和HIV-1病毒受体CD4(T淋巴细胞分化抗原)的作用机理.方法：人白介素-16的结构保守区由SYBYL软件中的Biopolymer模块建立，其非保守区由LOOP SEARCH方法建立.结果：人白介素-16首先形成二聚体，然后与CD4的二聚体进一步形成HIL-16与CD4的复合物二聚体。接着，该复合物二聚体通过二硫键(Cys31-Cys31)形成HIL-16与CD4复合物的四聚体。结论：该相互作用模型有助于推测白介素-16的作用机制，也有益于全新抗艾滋病药物的合理设计。
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电子轰击离子化气相质谱法测定人类血浆中的丙卡特罗
目的：建立一种简便灵敏的气相质谱法用于测定丙卡特罗的血药浓度。方法：采用电子轰击离子化气相质谱法，以丙咪嗪做内标，样品采用液-液萃取、衍生化处理，分离柱为毛细管柱，进样器和接口温度分别为280℃和250℃，载气(氦气)流速为0.8 mL·min-1，进样口选择脉冲不分流模式，离子源和四极杆的温度分别为230℃和150℃.结果：测定方法的检测限为5 ng·L-1；线性范围为10-10 000ng·L-1；日内(n=5)和日间(n=5)变异系数均小于10％，平均回收率为99.1％±1.3％.结论：本方法灵敏、简便，可用于丙卡特罗的药代动力学研究.
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HIV-共受体CCR5的三维结构及与其拮抗剂TAK 779相互作用的比较分子模拟
目的：研究HⅣ-1的共受体CCR5与其拮抗剂TAK779的相互作用机制。方法：用比较分子模拟方法建立CCR5受体的三维结构模型；通过量子化学计算得到TAK779分子的结构参数和优几何构型；用DOCK4.0程序将TAK779分子对接到CCR5受体的结合位点上。结果：通过分子力学优化得到了CCR5受体的三维结构模型，配体的结合口袋位于第三、五、六、七跨膜区，组成结合口袋的氨基酸残基主要为 Thr105、Leu107、Tyr108、Gly111、Phe112、Ser114、Cly115、Lys197、Glu283、Gly286、Met287、Cys290；TAK779与CCR5受体的相互作用方式为氢键、静电和疏水作用；配体与受体的结合能为-51.606 kcal/mol.结论：上述模型有助于进一步理解膜受体识别HIV-1病毒的分子机制并设计新的HTV-1抑制剂。
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CH50与脂多糖的巨噬细胞激活作用及抗肿瘤活性的比较
目的：将重组纤连蛋白多肽CH50的抗肿瘤活性及巨噬细胞激活作用与脂多糖(LPS)进行比较，分析CH50作为抗肿瘤多肽的药理作用特点.方法：一氧化氮(NO)以比色法进行检测；采用磷酸钙-DNA共沉淀法进行γ-干扰素(IFN-γ)体内基因转染；腹腔内接种黑色素瘤B16细胞并计数肿瘤结节数.结果：体外低浓度或单独作用时，CH50激活巨噬细胞产生NO的作用比LPS低10倍以上(P＜0.01).但在体外大于l mg·L-1浓度且与IFN-γ联合应用时，CH50促进巨噬细胞产生NO的作用与LPS相同(P＞0.05).CH50和LPS之间没有协同作用.CH50单用在体内抑制肿瘤生长的作用优于LPS(P＜0.01).CH50／IFN-γ亦比LPS／IFN-γ抑制肿瘤生长的作用更强.结论：与IFN-γ联合应用时，CH50对巨噬细胞的激活能力与LPS相同；但是CH50在体内具有更强的抑制小鼠黑色素瘤生长的作用.
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阿片孤儿受体三维结构的比较分子模拟
建立阿片孤儿受体(ORL1)的三维结构。方法：以蛙视紫红质为模板，用比较分子模拟方法进行序列联配，建立阿片孤儿受体七段跨膜区的结构；通过自己构件的数据库进行搜寻确立膜外环区的构象；对初始模型进行分子力学优化。结果：建立了阿片孤儿受体的三维结构模型；有多个氢键集中区分别存在于跨膜区和膜外环区；保守性的结合口袋位于第三、五、六、七跨膜区；预测可能的结合位点由包含Asp130、Tyr131残基的高度保守区和靠近膜外端的部分可变区组成。结论：模拟膜外环区的方法可用于其他GPCR的分子模拟；所建立的三维结构模型有助于阿片受体的结构功能研究并能为相关实验提供有益信息。
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CYP2D6在印度卡纳塔克邦和安得拉邦人群中的遗传多态性
AIM: To study the prevalence of cytochrome P-450 2D6 (CYP2D6) polymorphism in Karnataka ( KA ) and Andhra Pradesh (AP) population. METHODS: Two hundred and eleven healthy human volunteers participated in the study (100 from KA and 111 from AP). At bed time, after voiding their bladder, the volunteers ingested 30 mg of dextromethorphan hydrobromide (DM). Urine samples were collected for 8 h. DM and its metabolite dextrorphan (DT) were estimated in the urine using HPLC. The metabolic ratio (DM/DT) was used for phenotyping. RESULTS: The prevalence of poor metabolisers (PM) in KA is 4 ％ and AP is 1.8 ％.CONCLUSION: The frequency of PM phenotype in South Indian population is in between the Western and Oriental population.
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人肺泡上皮细胞株A549和脐静脉内皮细胞中的内皮素-1通路
AIM: This study was designed to characterize the endothelin pathway in an immortalized human adenocarcinoma-derived alveolar epithelial cell line (A549) and human umbilical vein endothelial cell line (HUVEC).METHODS: The release of ET-1 and big-ET-1 was measured in the incubation medium of both cell lines.The expression of mRNAs coding for the endothelin isoforms (hppET-1, -2, -3), the endothelin converting enzymes (hECE-la, b, c, and d) and the hETA and hETB receptors was investigated using RT-PCR. The expression of ECE-1 mRNA in various human tissues and in A549 cells was investigated by Northern blot analysis and the subcellular localization of ECE-1 in A549 cells was investigated by immunoblotting using a polyclonal antibody. RESULTS: Under control conditions, HUVEC release both ET-1 and big-ET-1 (ratio 5 to 1) while in A549 cells the big-ET-1 levels were below the threshold of detection. The release of these two peptides was minimally affected by various inhibitors of peptidases. However, in both cell lines phosphoramidon produced a concentration-dependent inhibition of ET-1 release and an enhanced accumulation of big-ET-1. Both HUVEC and A549 cells express the mRNAs for ppET-1, ET-A, and ET-B receptor subtypes and ECE-1 (isoforms ECE-lb, c and/or d). In addition, in HUVEC the mRNAs for ppET-2 and for the isoform ECE-la were also detected.In A549 cells, ECE-1 had a preferential subcellular localization in the membrane fraction but was not detected in the cytosol. CONCLUSION: Both A549 and HUVEC produce and release endothelin-1 through a specific enzymatic pathway, whether or not ECE-1 is the only enzyme involved remains to be determined. A549 might be used as a screening assay for drug discovery such as for inhibitors of endothelin-1 release.
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孤啡肽、内吗啡肽-1和-2与无脊椎动物免疫和神经系统的μ3阿片受体无相互作用
AIM: To determine if endomorphin-1,-2 and nociceptin (orphanin FQ) bind to the μ3 opiate receptor subtype or release nitric oxide as μ3 selective ligands do. METHODS: These opioid peptides were examined for their ability to displace [3H]dihydromorphine (DHM) binding from the invertebrate (immunocytes and pedal ganglia) μ3 opiate receptor in membrane homogenates. The ligands were also tested for their ability to release nitric oxide from the same intact tissues utilizing an amperometric probe that measures nitric oxide in real-time. RESULTS: Endomorphin-1,-2 and nociceptin do not displace [3H]DHM binding from immunocyte or pedal ganglia membrane homogenates nor do they release nitric oxide from these tissues. CONCLUSION: Since thesenewly discovered opioid peptides do not interact with the μ3 opiate receptor subtype, endogenous morphine's significance is enhanced because it appears to be the only naturally occurring opiate ligand for the receptor. Furthermore, since this study involves invertebrate tissues,this signal system had to evolve early during evolution.
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杏仁核内去甲肾上腺素在应激激素调控记忆保持过程中的作用
There is extensive evidence indicating that the noradrenergic system of the amygdala, particularly the basolateral nucleus of the amygdala (BLA), is involved in memory consolidation. This article reviews the central hypothesis that stress hormones released during emotionally arousing experiences activate noradrenergic mechanisms in the BLA, resulting in enhanced memory for those events. Findings from expenments using rats have shown that the memory-modulatory effects of the adrenocortical stress hormones epinephrine and glucocorficoids involve activation of β-adrenoceptors in the BLA. In addition, both behavioral and microdialysis studies have shown that the noradrenergic system of the BLA also mediates the influences of other neuromodulatory systems such as opioid peptidergic and GABAergic systems on memory storage. Other findings indicate that this stress hormone-induced activation of noradrenergic mechanisms in the BLA regulates memory storage in other brain regions.
| 年 | 期数 |
| 2018 | 01 02 03 04 05 06 07 08 09 10 11 12 |
| 2017 | 01 02 03 04 05 06 07 08 09 10 11 12 |
| 2016 | 01 02 03 04 05 06 07 08 09 10 11 12 |
| 2015 | 01 02 03 04 05 06 07 08 09 10 11 12 |
| 2014 | 01 02 03 04 05 06 07 08 09 10 11 12 |
| 2013 | 01 02 03 04 05 06 07 08 09 10 11 12 |
| 2012 | 01 02 03 04 05 06 07 08 09 10 11 12 |
| 2011 | 01 03 04 05 06 07 09 10 11 12 |
| 2010 | 01 02 03 04 05 06 07 08 09 10 11 12 |
| 2009 | 01 02 03 04 05 06 07 08 09 10 11 12 |
| 2008 | 01 02 03 04 05 06 07 08 09 10 11 12 |
| 2007 | 01 02 03 04 05 06 07 08 09 10 11 12 |
| 2006 | 01 02 03 04 05 06 07 08 09 10 11 12 |
| 2005 | 01 02 03 04 05 06 07 08 09 10 11 12 |
| 2004 | 01 02 03 04 05 06 07 08 09 10 11 12 |
| 2003 | 01 02 03 04 05 06 07 08 09 10 11 12 |
| 2002 | 01 02 03 04 05 06 07 08 09 10 11 12 |
| 2001 | 01 02 03 04 05 06 07 08 09 10 11 12 |
| 2000 | 01 02 03 04 05 06 07 08 09 10 11 12 |
| 1999 | 02 03 06 08 09 10 |
| 1998 | 01 03 04 |
| 1996 | 01 02 |
| 1995 | 03 05 |
| 1994 | 02 06 |
