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1.
为探讨腺苷A1受体与表皮生长因子受体(EGFR)之间的信号作用,阐明原代培养皮层神经元上腺苷A1受体介导的神经保护机制。采用原代培养大鼠皮层神经元缺氧损伤模型、免疫细胞化学、激光共聚焦显微镜观察、免疫共沉淀、Western Blot等方法在原代培养的大鼠皮层神经元和HEK293/A1R细胞上研究腺苷A1受体与表皮生长因子受体的相互作用方式,揭示由腺苷A1受体介导的神经保护机制。  相似文献   

2.
熊杰  黄俊华 《药学学报》1998,33(3):175-179
为进一步研究对羟吡啶甲基腺苷(HPMA)受体作用特点,用离体大鼠前列腺端输精管,比较了它与A1受体特异性激动剂环己烷基腺苷(CHA)作用异同。结果表明,HPMA有非A1受体样突触后抑制作用,能剂量依赖性地降低外源性PE,NE,ACh引起的输精管收缩反应;在场刺激下它优先作用于突触前;高剂量的HPMA(10-5mol·L-1)不仅可完全抑制场刺激引起的输精管收缩反应,同时还使组织对外源性ACh的反应性降低,是突触前抑制和突触后抑制的共同结果。提示HPMA在大鼠输精管同时具有突触前A1受体和突触后非A1受体作用。  相似文献   

3.
局部组织的缺血/缺氧常使细胞外腺苷浓度升高,腺苷通过细胞膜表面的受体将低氧的信号传入细胞内,使细胞启动低氧应对机制。腺苷受体的4种亚型在这个过程中发挥了不同的生理作用,该文是关于A1受体在保护细胞、促进免疫、调节血压及血糖等方面作用的综述。  相似文献   

4.
吴乐  谢守珍  李云庆 《医药导报》2004,23(11):0795-0798
腺苷受体是一类G蛋白耦联受体家族,有4个亚型,分别是A1、A2A、A2B、A3受体。腺苷受体广泛分布于神经系统,激活后在体内发挥不同的作用,如调节神经递质的释放、神经元的兴奋性、运动控制、情绪反应等。其中A1和A2A受体与痛信息的传递和调控密切相关,他们的选择性激动药和拮抗药具有良好的临床应用前景。因此,腺苷受体参与痛信息的传递和调控的机制成为人们关注和研究的焦点。  相似文献   

5.
Exendin-4与神经退行性疾病的关系   总被引:1,自引:1,他引:0  
Exendin-4是一种糖尿病新药,也是胰高血糖素样肽-1(GLP-1)类似物,能激活GLP-l受体,上调cAMP发挥生理活性。GLP-1受体与神经元可塑性及存活密切联系。Exendin-4还能激活多条信号通路,调节胞内钙离子(Ca2+)稳态,减轻兴奋性毒性,抑制细胞凋亡,促进神经元增生、分化,对神经退行性疾病有治疗作用。该文旨在阐明exendin-4的神经保护机制,为神经退行性疾病的预防与治疗提供新思路。  相似文献   

6.
由不同类哺乳动物克隆获得的腺苷A2A受体被生理浓度的腺苷激活,进而刺激cAMP一其它介质的形成,嗜中性白细胞、血小板和务砭中均发现这类受体,中枢神经系统中某些细胞内含量尤其丰富。尾状它们与多巴胺D2受体共存,A2A受体的兴奋造成D2受体介导的神经传递的减低,作用于A2A受体的药物,可用于修饰对神经和精神疾病有重要关系的多巴胺能神经传递。本文论述了近期开发的A2A受体拮抗剂怎样用来阐明被A2A受体  相似文献   

7.
目的观察腺苷A1受体激活在钙调磷酸酶(CaN)通路上对异丙肾上腺素(Iso)诱导的心肌细胞肥大的抑制作用及机制。方法体外培养大鼠乳鼠心肌细胞,以Iso 10μmol.L-1诱导心肌细胞肥大,观察腺苷A1受体激动剂R(-)-N6-(2-phenylIsopropyl)adenosine(R-PIA)1μmol.L-1对其作用,进一步探讨钙调神经磷酸酶特异性抑制剂环孢菌素A(CSA)1μmol.L-1、PKA抑制剂cAMP三乙胺盐(RP-cAMPS)1μmol.L-1、百日咳毒素(PTX)5 mg.L-1存在时,腺苷A1受体的激活对心肌细胞肥大的影响。通过Lowry法测心肌细胞蛋白含量;RT-PCR法检测心肌细胞心钠素(ANP)的mRNA表达;Western blot法测心肌细胞CaN的相对表达水平;以Fluo-3/AM为荧光探针,共聚焦显微镜下测量心肌细胞[Ca2+]i瞬变。结果 10μmol.L-1 Iso可以诱导心肌细胞肥大,腺苷A1受体激动剂R-PIA可以使其蛋白含量降低、ANP的mRNA表达减少、CaN相对表达降低、[Ca2+]i荧光强度减小,CSA、RP-cAMPS有类似抑制作用,PTX预处理的情况下,R-PIA对Iso诱导的心肌肥大的抑制作用消失。结论腺苷A1受体可以通过钙调磷酸酶通路抑制Iso诱导的心肌肥大,其机制与降低细胞内[Ca2+]i浓度及CaN表达有关。  相似文献   

8.
朱维娜  王晓辉  丁正年  刘莉  李跃华 《江苏医药》2012,38(12):1368-1370
目的探讨α-硫辛酸(LA)促进神经突触生长的可能机制。方法将体外培养的小鼠神经母细胞瘤N2a细胞分为对照组(A组)、细胞外信号调节蛋白激酶(ERK)抑制剂PD98059 40μM组(B组)、LA 500μM组(C组)和PD98059 40μM+LA 500μM组(D组)。用光学显微镜观察细胞突触生长情况,Western blot法检测ERK表达水平。结果与A组相比,C组突触生长、ERK激活水平增加(P<0.01);而D组能明显抑制C组上述观察指标的增加过程(P<0.01)。结论 LA对神经细胞突触生长的促进作用可能是通过激活ERK依赖性信号通路来实现的。  相似文献   

9.
《江苏医药》2012,38(12)
目的 探讨α-硫辛酸(LA)促进神经突触生长的可能机制.方法 将体外培养的小鼠神经母细胞瘤N2a细胞分为对照组(A组)、细胞外信号调节蛋白激酶(ERK)抑制剂PD98059 40μM 组(B组)、LA 500 μM组(C组)和PD98059 40μM+LA 500μM组(D组).用光学显微镜观察细胞突触生长情况,Western blot法检测ERK表达水平.结果 与A组相比,C组突触生长、ERK激活水平增加(P<0.01);而D组能明显抑制C组上述观察指标的增加过程(P<0.01).结论 LA对神经细胞突触生长的促进作用可能是通过激活ERK依赖性信号通路来实现的.  相似文献   

10.
压宁定即乌拉地尔是α1受体阻滞剂,其作用机理为选择性的阻断外周神经突触后的α1受体、兴奋中枢5-羟色胺-Ⅰ A受体、抑制交感神经张力、降低延髓血管中枢的反馈调节而使外周血管阻力下降,发挥周围和中枢降压作用,同时它还有轻微的β受体阻断作用,保留了突触前α2受体的负反馈机制,所以没有因血管扩张所导致的反射性心率加快现象,不增加心肌耗氧量,故临床上常用于治疗高血压危象及血压急骤升高、重度和极重度高血压及难治性高血压.  相似文献   

11.
环孢素A与CYP3A   总被引:9,自引:0,他引:9  
环孢霉素A是一种广泛用于器官移植的免疫抑制剂,其生物利用度低且个体差异大,本文从环孢霉素A代谢的影响因素、环孢霉素A与药物和食物的相互作用等方面探讨了环孢霉素A与CYP3A的关系。则时介绍了CYP3A活性的体内测定方法。  相似文献   

12.
The structures of leucomycin A4A5A6A7A8 and A9   总被引:1,自引:0,他引:1  
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16.
Bisphenol A (BPA) is used in the manufacture of polycarbonate and epoxy resin plastics. There has been interest in the possibility that BPA has immunotoxic properties, and a variety of investigations have explored this. Among the approaches taken have been human observational and cross-sectional studies, investigations using experimental animals, and in vitro studies, some of which have been reviewed previously by the European Food Safety Authority (EFSA).This commentary aims to provide a focused review of data regarding the ability of BPA to perturb the immune system, including the developing immune system, and to cause related adverse health effects. The objective is to complement the evaluations conducted by EFSA, with a focus on the ability of BPA to impair immune function, to promote respiratory allergy and airway inflammation, and to compromise immunological tolerance to dietary proteins.The conclusion drawn is that there is currently no persuasive evidence that BPA has significant immunotoxic potential. This is, in part, due to some of the data reviewed being apparently contradictory or inconsistent, and the investigations from which those data were derived having limitations with regard to experimental design.The conclusion drawn here is that presently there is no clear evidence that BPA has the potential to cause immunotoxicity resulting in adverse health effects.  相似文献   

17.
Antiviral activity of brefeldin A and verrucarin A   总被引:4,自引:0,他引:4  
  相似文献   

18.
A one-pot synthesis of ageladine A and analogues is reported. The key Pictet-Spengler reaction between 2-aminohistamine and aryl aldehydes has been successfully utilized for the synthesis of the natural product and 14 analogues. These compounds were screened for their matrix metalloprotease (MMP) and kinase inhibition to develop the first structure-activity relationship of ageladine A analogues. One compound, which showed significant kinase activity but little MMP inhibitory activity, was found to be highly active in an antiangiogenic screen, suggesting that the angiogenic activity of ageladine A is not associated with MMP inhibition but rather kinase inhibitory activity. Cytotoxicity was excluded as a mode of action by the assay of ageladine A and an analogue against 60 human cell lines.  相似文献   

19.
This review summarizes the current tendencies observed in the past 5 years in the development of A(1) and A(2A) adenosine receptor antagonists performed in various academia and industry. A(1) and A(2A) AR antagonists are as well xanthines as heteroaromatic derivatives and are most commonly 6:5 fused heteroatomic compounds. Among xanthine-based compounds, some common features could be pointed out. The recent A(1) AR ligands which show good biological profile, possess long alkyl chains in position 1 and 3 as well as bulky C(8)-substituent, while A(2A) AR antagonists with a high A(2A) AR affinity are C(8)-styryl substituted with N(1)-alkyl/alkynyl moiety or fused tricyclic xanthines possessing heteroatom(s) in the third cycle. The research in the field of heteroaromatic A(1) and A(2A) ARs antagonists impressively has a wide range. Ligands are as well non-fused monocyclic substituted compounds as fused bi- and tricyclic derivatives with the nitrogen, oxygen and sulfur heteroatoms. Most often, adenosine A(1) receptor non-xanthine antagonists are adenine-based, having substituted amino group and variable nitrogen atoms positions in the molecules. A(2A) AR ligands show good affinity when furanyl function, which is crucial for binding, is present in the fused bicyclic and tricyclic analogs. Moreover, tricyclic nitrogen containing antagonists in order to be active, frequently possess long-alkylphenyl moiety.  相似文献   

20.
《Substance use & misuse》2013,48(14):2185-2191
Numerous studies and clinical anecdotes reveal a relationship between attendance at A.A. meetings and/or degree of involvement in A.A. and maintenance of sobriety. Hypotheses as to how A.A. and/or the A.A. meeting is helpful to its members have ranged from a focus on factors common to all therapy groups, to aspects of A.A. “treatment” which are behavioral in nature. Presented here is another way of understanding A.A.'s effectiveness within the frame of more recent, constructivistic approaches to family therapy. In particular, the A.A. topic meeting is compared to the reflecting team concept of Tom Anderson.  相似文献   

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