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1.
Cannabinoid receptor Type 2(简称CB2)是大麻素受体的一种亚型,因为其无中枢神经副作用,不会产生成瘾性及耐受性,显示出了非常好的开发前景和潜在的应用价值。其作为免疫调节剂、神经保护剂和抗癌药等将具有巨大市场价值。目前,CB2蛋白的空间结构还未被测定出来,对于CB2的折叠问题研究也开展的较少,为了研究大麻素受体亚型蛋白CB2的折叠问题以及方便更多的研究人员对CB2空间结构和相关药理特性的研究,本文提出了一种基于HP模型的折叠求解方法。通过使用回溯机制和蒙特卡罗方法对此优化问题进行求解,算法可有效的在全局范围内进行寻找最优解,避免了掉入局部最优问题。实验结果表明,本文方法获取的CB2蛋白空间构象具有较低的能量值,折叠情况较好。  相似文献   

2.
The endocannabinoid system (ECS) is composed of cannabinoid receptors, their endogenous ligands, and the enzymes involved in endocannabinoid turnover. Modulating the activity of the ECS may influence a variety of physiological and pathophysiological processes. A growing body of evidence indicates that activation of cannabinoid receptors by endogenous, plant-derived, or synthetic cannabinoids may exert beneficial effects on gastrointestinal inflammation and visceral pain. The present ex vivo study aimed to investigate immunohistochemically the distribution of cannabinoid receptors CB1, CB2, G protein-coupled receptor 55 (GPR55), and peroxisome proliferation activation receptor alpha (PPARα) in the canine gastrointestinal tract. CB1 receptor immunoreactivity was observed in the lamina propria and epithelial cells. CB2 receptor immunoreactivity was expressed by lamina propria mast cells and immunocytes, blood vessels, and smooth muscle cells. Faint CB2 receptor immunoreactivity was also observed in neurons and glial cells of the submucosal plexus. GPR55 receptor immunoreactivity was expressed by lamina propria macrophages and smooth muscle cells. PPARα receptor immunoreactivity was expressed by blood vessels, smooth muscle cells, and glial cells of the myenteric plexus. Cannabinoid receptors showed a wide distribution in the gastrointestinal tract of the dog. Since cannabinoid receptors have a protective role in inflammatory bowel disease, the present research provides an anatomical basis supporting the therapeutic use of cannabinoid receptor agonists in relieving motility disorders and visceral hypersensitivity in canine acute or chronic enteropathies.  相似文献   

3.
2-Amino-5-aryl-pyridines, exemplified by compound 1, had been identified as a synthetically tractable series of CB2 agonists from a high-throughput screen of the GlaxoSmithKline compound collection. Described herein are the results of an investigation of the structure–activity relationships (SAR) which led to the identification a number of potent and selective agonists.  相似文献   

4.
采用RT-PCR获得黄瓜花叶病毒CMV-CB7株系全长基因组cDNA,经克隆测序发现该CMV的RNA1、2和3分别为3356nt、3045nt和2218nt(序列登录号为:EF216866、DQ785470和EF216867).CMV-CB7基因组cDNA克隆体外转录RNA接种心叶烟引起坏死症状,而CMV-Fny则产生典型花叶.由CMV-CB7和CMV-Fny基因组RNA相互交换而构建6个假重组型病毒(C1C2F3、C1F2C3、F1C2C3、F1F2C3、F1C2F3和C1F2C3)活性分析表明:CMV-CB7基因组RNA2决定其在寄主上的症状反应.嵌合型RNA2(RNA2F5C3和RNA2C3F5)的寄主侵染活性测定表明:2b基因或RNA23′端非编码序列决定CMV-CB7在心叶烟坏死症状.RNA印迹分析结果显示:CMV-CB7和CMV-FnyF5C3引起寄主坏死与基因组RNA积累没有直接关系.  相似文献   

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7.
SAR studies on a series of thiophene amide derivatives provided CB(2) receptor agonists. The activity of the compounds was characterized by radioligand binding determination, multiple functional assays, ADME, and pharmacokinetic studies. A representative compound with selectivity for CB(2) over CB(1) effectively produced analgesia in behavioral models of neuropathic, inflammatory, and postsurgical pain. Control experiments using a CB(2) antagonist demonstrated the efficacy in the pain models resulted from CB(2) agonism.  相似文献   

8.
本文介绍一种预测鼻咽癌放射敏感性的方法——CB微核法。以该法评介了鼻咽癌细胞株及20例鼻咽癌患者活检标本的放射敏感性,随着剂量增加,微核率也明显增加。CB微核的剂量-效应与克隆法的剂量效应呈高度负相关(r=-0.970)。活检标本微核实验表明,20例中8例反应较高,7例中等,5例反应偏 低;随访表明,反应偏低者中已有2例有复发倾向。由于CB微核法具有简便、快速、正确性较高等优点,适于临床应用。  相似文献   

9.
胶样菌CB39产海藻糖的研究   总被引:2,自引:0,他引:2  
从长白山天池水中筛选到一株低温条件下产糖的细菌。通过薄层层析、成脎反应、毛细管等速电泳以及红外光谱法确定该糖为海藻糖;经鉴定此菌株是胶样菌属中的一个新种(ColloidesSp.)定名为CB39;与已报道的产海藻糖菌株不同的是,菌株CB39能将产生的海藻糖分泌到细胞外,18℃时其培养液中海藻糖含量为2562mg/g干菌体;采用紫外诱变法筛选到一株在25℃条件下产海藻糖量为4167mg/g干菌体的高产突变株5,产糖量是同温度下野生菌的8倍。  相似文献   

10.

Background

The endogenous cannabinoid system is involved in the control of pain. However, little is known as to the integrity of the cannabinoid system in human pain syndromes. Here we investigate the expression of the cannabinoid receptor 1 (CB1) in human Achilles tendons from healthy volunteers and from patients with Achilles tendinosis.

Methodology

Cannabinoid CB1 receptor immunoreactivity (CB1IR) was evaluated in formalin-fixed biopsies from individuals suffering from painful Achilles tendinosis in comparison with healthy human Achilles tendons.

Principal Findings

CB1IR was seen as a granular pattern in the tenocytes. CB1IR was also observed in the blood vessel wall and in the perineurium of the nerve. Quantification of the immunoreactivity in tenocytes showed an increase of CB1 receptor expression in tendinosis tissue compared to control tissue.

Conclusion

Expression of cannabinoid receptor 1 is increased in human Achilles tendinosis suggesting that the cannabinoid system may be dysregulated in this disorder.  相似文献   

11.
一株高毒力致病杆菌CB6的鉴定   总被引:8,自引:0,他引:8  
从北京郊区果园采集的小卷蛾斯氏线虫(Steinernema carpocapsae)肠道内分离到一株具有较强杀虫和抑菌活性的致病杆菌菌株CB6。形态特征及生理生化特征测定结果表明,CB6菌株与致病杆菌属(Xenorhabdus)中的嗜线虫致病杆菌(X. nematophila)种的特征基本一致。测定了该菌株的16S rRNA序列并根据16S rRNA序列构建了系统发育树;在系统发育树中,CB6菌株与嗜线虫致病杆菌其他4个菌株形成一个类群,序列同源性大于99%。但CB6菌株的酪氨酸酶、脂酶(蛋黄)的产生、核糖产酸等生化特征与嗜线虫致病杆菌种内的其他菌株存在一定的差异,且具有更强的杀虫和抑菌活性。因此认为CB6菌株是嗜线虫致病杆菌的一个变种,命名为嗜线虫致病杆菌北京变种(X. nematophila var. pekingensis)。  相似文献   

12.
A series of α-amidosulfones were found to be potent and selective agonists of CB2. The discovery, synthesis, and structure–activity relationships of this series of agonists are reported. In addition, the pharmacokinetic properties of the most promising compounds are profiled.  相似文献   

13.
《菌物学报》2017,(6):743-751
前期工作中采用组织分离法分离、纯化得到一白腐真菌CB1,本研究进一步观察菌株CB1形态特征和培养特性,克隆菌株CB1的ITS基因序列,对菌株CB1的ITS序列进行同源性比对和系统进化分析,完成菌株CB1综合的鉴定。同时对菌株CB1脱色两种活性染料进行了研究,探讨菌株CB1脱色活性染料的能力。结果表明,菌株CB1形态特征和培养特性与一色齿毛菌Cerrena unicolor特征基本吻合,菌株CB1的系统进化分析表明菌株CB1的ITS序列与一色齿毛菌的ITS序列有较近的进化关系,形态学和分子生物学综合鉴定菌株CB1为C.unicolor CB1。染料脱色结果表明,菌株CB1可以明显脱色活性黑和活性红染料,与脱色活性黑相比,菌株CB1可以更有效地脱色活性红染料,在脱色12d时,菌株CB1对浓度为10、50、100、250、500mg/L的活性黑脱色率分别为96%、93%、65%、55%、40%,菌株CB1对浓度为10、50、100、250、500mg/L的活性红在12d时的脱色率分别为98%、95%、91%、87%、83%。  相似文献   

14.
The endocannabinoid CB2 receptor system has been implicated in the neuropathology of Alzheimer’s disease (AD). In order to investigate the impact of the CB2 receptor system on AD pathology, a colony of mice with a deleted CB2 receptor gene, CNR2, was established on a transgenic human mutant APP background for pathological comparison with CB2 receptor–sufficient transgenic mice. J20 APP (PDGFB-APPSwInd) mice were bred over two generations with CNR2−/− (Cnr2tm1Dgen/J) mice to produce a colony of J20 CNR2+/+ and J20 CNR2−/− mice. Seventeen J20 CNR2+/+ mice (12 females, 5 males) and 16 J20 CNR2−/− mice (11 females, 5 males) were killed at 12 months, and their brains were interrogated for AD-related pathology with both biochemistry and immunocytochemistry (ICC). In addition to amyloid-dependent endpoints such as soluble Aβ production and plaque deposition quantified with 6E10 staining, the effect of CB2 receptor deletion on total soluble mouse tau production was assayed by using a recently developed high-sensitivity assay. Results revealed that soluble Aβ42 and plaque deposition were significantly increased in J20 CNR2−/− mice relative to CNR2+/+ mice. Microgliosis, quantified with ionized calcium-binding adapter molecule 1 (Iba-1) staining, did not differ between groups, whereas plaque associated microglia was more abundant in J20 CNR2−/− mice. Total tau was significantly suppressed in J20 CNR2−/− mice relative to J20 CNR2+/+ mice. The results confirm the constitutive role of the CB2 receptor system both in reducing amyloid plaque pathology in AD and also support tehpotential of cannabinoid therapies targeting CB2 to reduce Aβ; however, the results suggest that interventions may have a divergent effect on tau pathology.  相似文献   

15.
The endocannabinoid CB2 receptor system has been implicated in the neuropathology of Alzheimer’s disease (AD). In order to investigate the impact of the CB2 receptor system on AD pathology, a colony of mice with a deleted CB2 receptor gene, CNR2, was established on a transgenic human mutant APP background for pathological comparison with CB2 receptor–sufficient transgenic mice. J20 APP (PDGFB-APPSwInd) mice were bred over two generations with CNR2−/− (Cnr2tm1Dgen/J) mice to produce a colony of J20 CNR2+/+ and J20 CNR2−/− mice. Seventeen J20 CNR2+/+ mice (12 females, 5 males) and 16 J20 CNR2−/− mice (11 females, 5 males) were killed at 12 months, and their brains were interrogated for AD-related pathology with both biochemistry and immunocytochemistry (ICC). In addition to amyloid-dependent endpoints such as soluble Aβ production and plaque deposition quantified with 6E10 staining, the effect of CB2 receptor deletion on total soluble mouse tau production was assayed by using a recently developed high-sensitivity assay. Results revealed that soluble Aβ42 and plaque deposition were significantly increased in J20 CNR2−/− mice relative to CNR2+/+ mice. Microgliosis, quantified with ionized calcium-binding adapter molecule 1 (Iba-1) staining, did not differ between groups, whereas plaque associated microglia was more abundant in J20 CNR2−/− mice. Total tau was significantly suppressed in J20 CNR2−/− mice relative to J20 CNR2+/+ mice. The results confirm the constitutive role of the CB2 receptor system both in reducing amyloid plaque pathology in AD and also support tehpotential of cannabinoid therapies targeting CB2 to reduce Aβ; however, the results suggest that interventions may have a divergent effect on tau pathology.  相似文献   

16.
嗜线虫致病杆菌CB6菌株培养特性的初步研究   总被引:2,自引:0,他引:2  
研究了嗜线虫致病杆菌(Xenorhabdus nematophila)CB6菌株的菌体增殖规律及对主要营养成分的利用规律。结果表明,该菌延缓期、对数生长期、稳定期、衰亡期分别为0~6h、6~18h、18~48h和48h以后。培养18h时,糖和蛋白质的含量达到最低并保持稳定;氨基氮含量在6h时最低,以后逐渐升高,36h达到最高。药效实验表明,该菌培养42h时其菌悬液杀虫活性最高。  相似文献   

17.
Exogenous and endogenous cannabinoids play an important role in modulating the release of neurotransmitters in hippocampal excitatory and inhibitory networks, thus having profound effect on higher cognitive and emotional functions such as learning and memory. In this study we have studied the effect of cannabinoid agonists on the potassium depolarization-evoked [(3)H]GABA release from hippocampal synaptosomes in the wild-type (WT) and cannabinoid 1 receptor (CB(1)R)-null mutant mice. All tested cannabinoid agonists (WIN55,212-2, CP55,940, HU-210, 2-arachidonoyl-glycerol, 2-AG; delta-9-tetra-hydrocannabinol, THC) inhibited [(3)H]GABA release in WT mice with the following rank order of agonist potency: HU-210>CP55,490>WIN55,212-2>2-AG>THC. By contrast, 2-AG and THC displayed the greatest efficacy eliciting almost complete inhibition of evoked [(3)H]GABA efflux, whereas the maximal inhibition obtained by HU-210, CP55,490, and WIN55,212-2 were less, eliciting not more than 40% inhibition. The inhibitory effect of WIN55,212-2, THC and 2-AG on evoked [(3)H]GABA efflux was antagonized by the CB(1) receptor inverse agonist AM251 (0.5 μM) in the WT mice. In the CB(1)R knockout mice the inhibitory effects of all three agonists were attenuated. In these mice, AM251 did not antagonize, but further reduced the [(3)H]GABA release in the presence of the synthetic agonist WIN55,212-2. By contrast, the concentration-dependent inhibitory effects of THC and 2-AG were partially antagonized by AM251 in the absence of CB(1) receptors. Finally, the inhibition of evoked [(3)H]GABA efflux by THC and 2-AG was also partially attenuated by AM630 (1 μM), the CB(2) receptor-selective antagonist, both in WT and CB(1) knockout mice. Our data prove the involvement of CB(1) receptors in the effect of exo- and endocannabinoids on GABA efflux from hippocampal nerve terminals. In addition, in the effect of the exocannabinoid THC and the endocannabinoid 2-AG, non-CB(1), probably CB(2)-like receptors are also involved.  相似文献   

18.
化学修饰对金顶侧耳多糖抗病毒(CB5)活性的影响   总被引:12,自引:0,他引:12  
从金侧耳子实体中分离纯化一半乳甘露聚糖PC-3,其分子量约为67KD,一级结构a(1→6)糖苷键相连的Gal构成分子的主链,部份残基C2上带有分支,分支结构为a(1-2)Man-a(1-2)Man。按高碘酸氧化、部份酸水解、甲基化、硫酸程序对PC-3的结构进行化学修饰;并分别将PC-3及其衍生物与柯萨厅病毒B5进行体外实验,结果表明,PC-3经硫酸化后,显著地提高了抗病毒活性;而高碘酸氧化,甲基化  相似文献   

19.
Cannabinoid CB1 receptor (CB1R) activation decreases synaptic GABAergic and glutamatergic transmission and it also controls peripheral metabolism. Here we aimed at testing with 13C NMR isotopomer analysis whether CB1Rs could have a local metabolic role in brain areas having high CB1R density, such as the hippocampus. We labelled hippocampal slices with the tracers [2-13C]acetate, which is oxidized in glial cells, and [U-13C]glucose, which is metabolized both in glia and neurons, to evaluate metabolic compartmentation between glia and neurons. The synthetic CB1R agonist WIN55212-2 (1 μM) significantly decreased the metabolism of both [2-13C]acetate (−11.6 ± 2.0%) and [U-13C]glucose (−11.2 ± 3.4%) in the tricarboxylic acid cycle that contributes to the glutamate pool. WIN55212-2 also significantly decreased the metabolism of [U-13C]glucose (−11.7 ± 4.0%) but not that of [2-13C]acetate contributing to the pool of GABA. These effects of WIN55212-2 were prevented by the CB1R antagonist AM251 (500 nM). These results thus suggest that CB1Rs might be present also in hippocampal astrocytes besides their well-known neuronal localization. Indeed, confocal microscopy analysis revealed the presence of specific CB1R immunoreactivity in astrocytes and pericytes throughout the hippocampus.In conclusion, CB1Rs are able to control hippocampal intermediary metabolism in both neuronal and glial compartments, which suggests new alternative mechanisms by which CB1Rs control cell physiology and afford neuroprotection.  相似文献   

20.
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