用嗅觉去感受世界--2004年诺贝尔生理学或医学奖成果简介

嗅觉系统对我们的生活非常重要，人类和其它哺乳动物利用嗅觉系统可以识别环境中巨大数量的化学物质。嗅觉是如何产生的？为解开这个难题，美国两位科学家阿克塞尔和巴克从编码气味受体的基因入手，发现了识别气味分子的受体，并且证明了嗅觉系统的组织方式，从而告诉世界我们是如何感受气味的。为表彰两人的贡献，Karolinska医学院诺贝尔奖评审委员会决定授予他们2004年诺贝尔生理学或医学奖。介绍了两位科学家是如何破解这个难题的。     

受体缺乏改变小鼠脑内组胺含量及昼夜节律

在乙谜麻醉下,分别于明时(8:00 a.m.)及暗时(8:00 p.m.)断头处死野生型及组胺H1R基因敲除型小鼠,迅速取出脑组织并分离出皮层、纹状体、海马、下丘脑、丘脑、中脑及脑干等脑区.这些脑组织被制成匀浆并用HPLC荧光检测法测量其组胺含量.结果显示暗时处死时,H1R基因敲除型小鼠海马、丘脑、中脑及脑干中的组胺含量明显低于野生型小鼠.明时处死时,野生型小鼠各脑区组胺含量均较暗时处死显著降低,但这一变化在H1R基因敲除型小鼠中并未观察到.这些表明作为组胺的功能靶,H1R不仅介导组胺的功能,而且调节大脑中组胺含量与释放的昼夜节律.     

Snake venom components and their applications in biomedicine

Snake envenomation is a socio-medical problem of considerable magnitude. About 2.5 million people are bitten by snakes annually, more than 100,000 fatally. However, although bites can be deadly, snake venom is a natural biological resource that contains several components of potential therapeutic value. Venom has been used in the treatment of a variety of pathophysiological conditions in Ayurveda, homeopathy and folk medicine. With the advent of biotechnology, the efficacy of such treatments has been substantiated by purifying components of venom and delineating their therapeutic properties. This review will focus on certain snake venom components and their applications in health and disease. Received 6 July 2006; received after revision 14 August 2006; accepted 28 September 2006     

Liver X receptors in cardiovascular and metabolic disease

Liver X receptors (LXRs) α and β are nuclear oxysterol receptors and metabolic sensors initially found to regulate cholesterol metabolism and lipid biosynthesis. Recent studies have elucidated the importance of LXR in the development of cardiovascular diseases and metabolic disorders. LXR agonists prevent development of atherosclerosis by modulation of metabolic as well as inflammatory gene expression in rodent models. Moreover, LXR activation inhibits hepatic gluconeogenesis and lowers serum glucose levels, indicating possible application of LXR activation in the treatment of diabetes mellitus. However, first-generation LXR agonists elevate hepatic and serum trigylceride levels, making subtype-specific agonists and selective LXR modulators rather than unselective LXR agonists a potential pharmacological strategy. This review summarizes the multiple physiological and pathophysiological implications of LXRs and observations that identify LXRs as potential targets for therapeutic interventions in human cardiovascular and metabolic disease. Received 30 August 2005; received after revision 10 October 2005; accepted 4 November 2005     

Natural sweet macromolecules: how sweet proteins work

A few proteins, discovered mainly in tropical fruits, have a distinct sweet taste. These proteins have played an important role towards a molecular understanding of the mechanisms of taste. Owing to the huge difference in size, between most sweeteners and sweet proteins, it was believed that they must interact with a different receptor from that of small molecular weight sweeteners. Recent modelling studies have shown that the single sweet taste receptor has multiple active sites and that the mechanism of interaction of sweet proteins is intrinsically different from that of small sweeteners. Small molecular weight sweeteners occupy small receptor cavities inside two subdomains of the receptor, whereas sweet proteins can interact with the sweet receptor according to a mechanism called the ‘wedge model’ in which they bind to a large external cavity. This review describes these mechanisms and outlines a history of sweet proteins. Received 11 February 2006; received after revision 31 March 2006; accepted 11 May 2006     

Nitric oxide mediates histamine induced down-regulation of H<Subscript>2</Subscript> receptor mRNA and internalization of the receptor protein (R1)

During agonist-dependent long-term stimulation of cells, histamine receptor subtypes are frequently down-regulated. However, the mechanisms underlying the modulation of receptor expression during long-term histamine stimulation have yet to be resolved. Based on our recently reported results showing an H₁-mediated down-regulation of histamine H₂ receptor mRNA in endothelial cells, our aim was to characterize the mechanism controlling rapid and long-term histamine-mediated modulation of H₂ receptor expression in more detail. We were able to show that the histamine-induced down-regulation of H₂ receptor mRNA and cell surface expression lasting for 24 h was accompanied by augmentation of the receptor protein level in the cytoplasmatic fraction of endothelial cells for this time period. Furthermore, changes in receptor protein levels in whole-cell lysate were negligible, indicating that the rapid and prolonged modulation of cell surface H₂ receptor levels by histamine was regulated solely via internalization. The role of nitric oxide (NO) as a key mediator in histamine-stimulated cell responses was underlined by subsequent studies showing the attenuation of histamine-induced H₂ receptor mRNA down-regulation and protein trafficking following NO synthase isozyme inhibition.Received 11 March 2003; received after revision 11 June 2003; accepted 17 June 2003     

钙依赖型蛋白激酶在ABA调控的杨树气孔运动中的作用

群众杨叶片下表皮经过植物激素脱落酸(ABA)和钙依赖型蛋白激酶抑制剂三氟拉嗪(TFP)处理后,在扫描电镜下观察了气孔开度的变化,并用透射电镜结合X-射线能谱显微分析技术,对保卫细胞内的K~ 、Ca~(2 )含量进行了研究。结果表明:ABA几乎完全抑制光照条件下叶片气孔的开放,而同时加入TFP则显著降低ABA对气孔开放的抑制作用。在ABA作用下,保卫细胞细胞质中的K~ 含量下降但Ca~(2 )含量增加;而同时加入TFP则可逆转ABA对K~ 、Ca~(2 )的作用。研究结果证明,钙依赖型蛋白激酶可能通过对保卫细胞内K~ 、Ca~(2 )的调节作用而介导了ABA调控气孔运动的信号转导过程。     

DRD3基因多态性与精神分裂症的相关性研究

目的 :研究多巴胺D3受体 (DRD3)基因的多态性与精神分裂症的关系。方法 :应用PCR -RFLP技术 ,在90名无亲缘关系的正常汉族人和80名精神分裂症患者中对DRD3基因第一外显子内Ser9Gly多态性进行分析。结果 :正常汉族人群中 ,DRD3等位基因1(Ser)和2(Gly)的频率分别为0.71和0.29。在正常对照组和精神分裂症组之间 ,等位基因频率 (X2=0.02,υ=1,P>0.05)和各种基因型 (P值均大于0.05)分布无显著性差异。结论 :DRD3基因的Ser9Gly多态性与中国汉族人群精神分裂症不相关。     

5-HTR2A基因 102T/C多态性与精神分裂症的相关性研究

目的 :探讨5 -羟色胺2A受体(5 -HTR2A)基因102T/C的多态性与精神分裂症的关系。方法 :应用PCR -RFLP技术 ,在90名无亲缘关系的大理地区正常汉族人和80名精神分裂症患者中对5 -羟色胺受体基因102T/C多态性进行分析。结果 :在正常对照组和精神分裂症组之间 ,等位基因频率 ( χ2=0.01,P>0.05)和各种基因型 (P值均大于0.05)分布无显著性差异。结论 :5 -羟色胺受体基因102C/T的多态性与汉族人群精神分裂症不相关。     

子宫内膜异位症的子宫内膜雌激素受体和孕激素受体mRNAs的表达

目的 :探讨雌激素受体 (ER)和孕激素受体 (PR)在子宫内膜异位症 (内异症 )子宫内膜的表达。方法 :利用大鼠内异症动物模型 ,采用逆转录聚合酶链反应 (RT -PCR)技术 ,检测子宫内膜ER和PRmRNAs的表达情况。结果 :内异症模型组大鼠异位内膜ER、PRmRNAs的表达低于在位内膜和对照组正常子宫内膜 ,与后两者比较差异有显著性意义 (P <0 0 1) ;而模型组在位内膜ER、PRmRNAs的表达与正常对照组比较差异无显著性意义 (P >0 0 5 )。内异症模型组异位内膜ER/PRmRNA大于在位内膜和正常子宫内膜ER/PRmRNA(P <0 0 1)。结论 :内异症大鼠异位内膜ERmRNA表达的相对增高在内异症的发生与发展中起着一定的作用