中华鳖心的肾上腺素能受体类型

采用改良的八木氏插管法在３２个离体灌流的鳖心上，重点研究了对３种肾上腺素能受体激动剂的变时性反应．其亲和力顺序：ＩＳＯ＞Ｅ≥ＮＥ．ＮＥ（３．３３×１０－８ｇ）的正变时性作用可被ＰＲＯ（３．３３×１０－６ｇ）所阻断，ＰＨＥＮＴ（３．３３×１０－６ｇ）则无效．同浓度（３．３３×１０－８ｇ）的Ｅ与ＮＥ正变时性作用相近，明显强于ＳＡＬ．选择性α－受体激动剂ＭＥＴＨＯ无明显作用或略抑制．夏季与冬季的鳖心反应基本相同．提示鳖心的肾上腺素能受体主要为β－亚型而无α－受体．     

大鼠海马CA1区β2肾上腺素能受体激活抑制晚期相长时程增强

海马在陈述性学习和记忆中起关键作用,海马内长时程增强(long-term potentiation,LTP)被认为是学习和记忆的突触机制.β肾上腺素能受体(β受体)在海马中大量分布.实验室先前工作表明,在CA1和CA3区,β1受体和β2受体有不同的亚细胞分布.大量的研究工作证实了β1受体在LTP中的重要作用,而关于β2受体在LTP中的作用所知甚少.研究应用在体场电位记录方法,研究β2受体激活对CA1区LTP的影响.实验结果表明,CA1区内给予β2受体激动剂Clenbuterol(10 ng)能显著抑制晚期相LTP,但对早期相LTP没有显著效应;Clenbuterol对晚期相LTP的抑制效应能被β2受体拮抗剂ICI 118551所逆转.这些结果提示,海马CA1区内β2受体的激活抑制晚期相LTP的维持.     

β2肾上腺素能受体基因多态性相关研究进展

回顾并总结近年来有关β2-AR单核苷酸多态性及其与人类心血管病关系的研究。     

4种钙离子检测／成像系统检测细胞胞浆钙振荡的比较

胞浆钙离子浓度的规律性增加,已经在动物、植物、微生物等许多重要生命活动中得以证明,如肌肉收缩、细胞分泌、卵子授精、神经传导、个体发育、细胞凋亡以及病原生物（寄生虫、细菌、病毒）对哺乳动物细胞的侵袭过程中的重要性,已经得到广泛认可．因此,活细胞不同微区中钙离子浓度规律性变化的成像研究已受到越来越多的关注．虽然目前多个厂家可以提供钙离子成像系统,但用户在根据需要进行选择时,往往得不到有关设备的足够信息,因此很难做出正确的选择．文中详细比较了4种不同配置的钙离子浓度测量系统在检测胰腺腺泡细胞和肝脏实质细胞胞浆钙离子浓度的振荡样增加时的性能差异,分析了这些差异的原因及解决方法,为钙离子成像系统的使用者和制造商提供参考信息．     

β2肾上腺素能受体基因多态性与支气管哮喘的关系

支气管哮喘是一种与遗传有关的I型超敏反应性疾病,其发生受多个基因及环境因素的共同影响,长期以来,β2肾上腺素能受体功能在哮喘发病中的地位一直备受关注,随着分子生物学技术的发展,人们可以从基因水平上探讨二者之间的关系.     

基于细胞的β2肾上腺素能受体激动剂功能性筛选体系在中草药中的应用

为了建立基于细胞的β2肾上腺素能受体激动剂筛选体系,将大鼠β2受体基因克隆人pcDNA3.1载体.转染具有cAMP应答元件调控的绿色荧光蛋白报告基因的中国仓鼠卵巢细胞(CHO),从得到的阳性单克隆细胞中筛选得到一个稳定表达β2受体,并且在受到激动剂刺激后发出剂量依赖绿色荧光强度的细胞株.将此筛选体系用于从中药中筛选具有β2受体激动剂活性的化合物.从几种芸香科药材中得到了辛弗林(synephine),从细辛和附子中得到了去甲乌药碱(higenamine),首次从受体水平证明了它们的β2激动剂活性.此筛选体系适合从大量天然化合物中快速筛选具有β2激动剂活性的成分.     

新疆哈萨克族β2肾上腺素能受体基因C659G变异与血清甘油三酯水平之间的关系

目的：研究人类β2肾上腺素能受体（ADRβ2）基因C659G变异与新疆哈萨克族甘油三酯水平间的关系．方法：采用多聚酶链式反应法及限制性内切酶片段长度多态性技术（PCR—RFLP）,对435例新疆哈萨克族人进行ADR＆基因C659G多态性检测,观察基因型和等位基因的分布频率及其与血清甘油三酯水平的关系．结果：435例哈萨克族人ADRβ2基因C659G基因型频率分别为CC85．747％、CG13．793％、GG0．64％,等位基因频率分别为C7．356％、G92．644％,分布符合Hardy—Weinberg定律．按照年龄分组后通过协方差分析扣除体重指数、平均动脉压对血清TG的影响后,可以看到各年龄分组中CG＋GG组与CC组血清TG水平均无统计学意义．结论：新疆哈萨克族人β2AR基因C659G多态性与血清甘油三酯水平无关．     

兔回肠纵肌肾上腺素能爱体作用分析及递质间的相互作用

实验采用兔离休回肠纵肌标本，观察了经典递质去甲肾上腺素（ＮＥ．）和乙酰胆碱（ＡＣｈ．）对兔回肠纵肌收缩的效应及其相互关系，并对其作用的受体途径进行了分析．实验结果表明；（１）ＡＣｈ能加强回肠纵肌收缩，ＮＥ有抑制作用，但二者的作用可以变化；（２）酚妥拉明使收缩力量增加，心得安使其减弱；（３）ＮＥ能加强Ａｃｈ的兴奋作用，这一加强作用可放心得安阻断．ＡＣｈ对ＮＥ的抑制作用无明显影响．以上结果提示，兔回肠纵肌α肾上腺素能受体介导抑制，β受体介导兴奋，ＮＥ加强Ａｃｈ的兴奋效应与β受体密切相关．     

视黄素受体介导的视黄素（retinoids）抗癌作用

对近年来视黄素受体介导视黄素抗癌作用机理的研究进展作一综述,主要有：1）视黄素受体;2）视黄素受体与细胞生长;3）视黄素受体与孤生受体的的相关性;4）视黄素受体对AP-1活性的抑制作用;5）视黄素受体介导的信号转导途径。通过研究,对于探讨视黄素受体的功能、阐明视黄素的抗癌机理、合成更多的受体选择性视黄素具有重要的现实意义。     

Lithium inhibits adrenergic and cholinergic increases in GTP binding in rat cortex

Lithium is a unique drug with therapeutic as well as prophylactic value for both manic and depressive phases of manic-depressive illness. The precise mechanisms of its clinical efficacy remain unknown, but there are two main theories of its biochemical action. One proposes that lithium inhibits adrenergically activated adenylate cyclase function whereas the other suggests that it inhibits phosphatidyl inositol turnover, which is known to be activated by cholinergic agonists. Neither mechanism alone, however, can explain both the antimanic and antidepressant effects of lithium. Because of the pivotal role of G proteins in post-receptor information transduction, we have investigated the interaction of lithium with G protein function. Lithium at therapeutically efficacious concentrations completely blocked both adrenergic and cholinergic agonist-induced increases in [3H]GTP binding to membranes from rat cerebral cortex, in both in vitro and ex vivo experiments. The same lithium treatments also abolished guanine nucleotide modulation of agonist binding. Our findings suggest G proteins (Gs and Gi or Go) as the molecular site of action for both the antimanic and antidepressant effects of lithium.     

Houart-Dupont钙振荡模型的复杂动态

运用中心流形定理和分岔理论分析了Houart-Dupont钙振荡模型的非线性动态,包括随参数变化时平衡点的类型及其稳定性的变化,从理论上严格证明了系统振荡现象产生与消失是由于平衡点发生了2次supercritical Hopf分岔导致的。通过运用matlab软件进行数值模拟,验证了理论分析结果的正确性。     

Repetitive transient rises in cytoplasmic free calcium in hormone-stimulated hepatocytes

In the stressed animal, the vasoactive hormones vasopressin and angiotensin-II and the neurotransmitter noradrenaline induce liver cells to release glucose from glycogen. The intracellular signal that links the cell-surface receptors for noradrenaline (alpha 1) and vasoactive peptides to activation of glycogenolysis is known to be a rise in the cytoplasmic concentration of free calcium ions (free Ca). The receptors for these agonists induce the hydrolysis of phosphatidylinositol 4,5-bisphosphate, a minor plasmalemma lipid, to produce inositol trisphosphate and diacylglycerol. Inositol trisphosphate has been shown to mobilize intracellular calcium in hepatocytes. We show here, by means of aequorin measurements in single, isolated rat hepatocytes, that the free Ca response to these agonists consists of a series of transients. Each transient rose within 3 s to a peak free Ca of at least 600 nM and had a duration of approximately 7 s. The transients were repeated at intervals of 0.3-4 min, depending on agonist concentration. Between transients, free Ca returned to the resting level of approximately 200 nM. Clearly, the mechanisms controlling free Ca in hepatocytes are more complex than hitherto suspected.     

Postsynaptic NMDA receptor-mediated calcium accumulation in hippocampal CA1 pyramidal cell dendrites

In the CA1 hippocampal region, intracellular calcium is a putative second messenger for the induction of long-term potentiation (LTP), a persistent increase of synaptic transmission produced by high frequency afferent fibre stimulation. Because LTP in this region is blocked by the NMDA (N-methyl-D-aspartate) receptor antagonist AP5 (DL-2-amino-5-phosphonovaleric acid) and the calcium permeability of NMDA receptors is controlled by a voltage-dependent magnesium block, a model has emerged that suggests that the calcium permeability of NMDA receptor-coupled ion channels is the biophysical basis for LTP induction. We have performed microfluorometric measurements in individual CA1 pyramidal cells during stimulus trains that induce LTP. In addition to a widespread component of postsynaptic calcium accumulation previously described, we now report that brief high frequency stimulus trains produce a transient component spatially localized to dendritic areas near activated afferents. This localized component is blocked by the NMDA receptor antagonist AP5. The results directly confirm the calcium rise predicted by NMDA receptor models of LTP induction.     

Agar coating in multicellular spheroids culture of rat hepatocytes

Aggregation of freshly isolated adult rat hepatocytesin vitro is important for the construction of artificial liver support system. In the experiment, agar has been used as an extracellular matrix substrate and results demonstrate that hepatocytes in serum-free culture medium can effectively form floating spheroids in tissue culture dishes coated with agar, which maintain higher ability to produce urea and albumin than monolayer cultured cells.     

Modulation of synchronous calcium oscillations in hippocampal neurons by photostimulation of astrocytes with femtosecond laser

A large body of evidence indicates that astrocytes play an important role in a range of brain functions through calcium (Ca²⁺) signaling. Experimentally evoking Ca²⁺ signaling is a useful technique for investigating the functions of astrocytes. However, conventional stimulation methods typically have poor spatio-temporal precision, and some are invasive. Our group has developed a technique to overcome these problems, in which astrocytes are photostimulated with a femtosecond laser. In the current study, we applied this method to a hippocampal neural network to explore astrocytic functions in detail. The results revealed that applying photostimulation to astrocytes in a cultured hippocampal astrocyte-neuron network caused the following changes: (i) Synchronous Ca²⁺ oscillations in neurons were induced; (ii) spontaneous Ca²⁺ synchrony instantaneously emerged; and (iii) high-frequency spontaneous Ca²⁺ synchrony was regulated. Thus, astrocytic Ca²⁺ signaling evoked by photostimulation was found to modulate synchronous Ca²⁺ oscillations in hippocampal neurons. We propose that photostimulation with a femtosecond laser will serve as a powerful tool in investigating astrocytic functions at the network level.     

富硒螺旋藻对肝叶切除大鼠肝细胞的抗氧化作用

目的:探讨富硒螺旋藻(Se-SP)对大鼠肝叶切除术后肝细胞的抗氧化效应。方法:采用W istar大鼠复制67%肝切除模型,3个不同剂量组的大鼠于术前连续7 d按每天每公斤体质量灌胃150 mg(H)、50 mg(M)、15 mg(L)的Se-SP,另设生理盐水(P)和假手术(F)对照组。在手术前(0h)及术后12 h和48 h等不同时间点取大鼠肝细胞,检测肝细胞中硒(Se)、脂质过氧化产物丙二醛(MDA)浓度以及谷胱甘肽过氧化物酶(GPx)和超氧化物歧化酶(SOD)活性。结果:与P、F组相比,H、M组肝细胞中Se、GPx和SOD水平均明显升高(P<0.05),MDA水平则明显降低(P<0.05);Se水平与GPx活性呈明显正相关(R2=0.75,P<0.05)而与MDA呈明显负相关(R2=0.70,P<0.05)。结论:Se-SP对肝切除大鼠肝细胞具有良好的抗氧化保护效应,对GPx活性具有明显上调作用。     

An N-methylaspartate receptor-mediated synapse in rat cerebral cortex: a site of action of ketamine?

It has been proposed that three major receptor subtypes subserve the putative transmitter role of glutamate and aspartate in the mammalian central nervous system. One subtype is classified by the specific agonist N-methylaspartate (NMA) and the specific antagonist 4-amino-2-phosphonovaleric acid. It has been shown recently that excitation of neurones by NMA is also selectively reduced by dissociative anaesthetics such as ketamine and phencyclidine and by sigma opiates, drugs of abuse with common psychotomimetic properties. Responses to NMA have an unusual voltage relation which may result from a voltage-dependent block of the activated channel by physiological concentrations of magnesium. No synaptic potential with properties similar to those of responses to NMA, however, has yet been reported. We describe here an excitatory postsynaptic potential (e.p.s.p.) evoked by electrical stimulation of the white matter and recorded intracellularly from pyramidal cells in slices of rat somatosensory cortex. This e.p.s.p. has the appropriate voltage relation and sensitivity to Mg2+ and ketamine to be an NMA receptor-mediated synapse and a potential central site for the psychotomimetic actions of ketamine.