凝血酶受体研究进展

凝血酶(thrombin,Ⅱa)作为一种丝氨酸蛋白酶,不仅在凝血瀑布反应中发挥作用,而且能够和包括神经细胞在内的多种细胞发生反应,并影响其行为。Ⅱa如此广泛的生理效应大部分由凝血酶受体(thrombin receptor,TR)介导。越来越多的证据表明,有新的受体参与介导凝血酶的功能。本文综述了已克隆的凝血酶受体的功能,并对可能存在的新的凝血酶受体作一初步探讨。     

胃肠癌雌激素受体和孕激素受体的表达及意义

用免疫组化Ｓ－Ｐ法检测７０例胃肠癌及胃肠炎患者胃肠粘膜的雌激素受体（ＥＲ）、孕激素受体（ＰＲ）。结果显示胃癌ＥＲ阳性率５２％，ＰＲ阳性率４４％，其中双阳性２４％；大肠癌ＥＲ阳性率４８％，ＰＲ阳性率４４％，其中双阳性３０％；而胃炎组织无ＥＲ及ＰＲ表达，结直肠炎只１例ＥＲ阳性。胃肠癌组与炎症组的ＥＲ、ＰＲ表达有非常显著差异（Ｐ〈０．０１）。按分化程度比较，ＥＲ和／或ＰＲ在低分化癌及中高分化癌中的阳性率     

血清转铁蛋白受体

本文细胞转铁蛋白受体和血清转铁蛋白受体的结构与理化特性，血清转铁蛋白的检测方法及其正常值，以及对机体铁状态和造血功能的评估，孕期缺的监测，缺铁性贫血与其他疾病所致贫血的鉴别等问题进行文献综述。     

转铁蛋白受体及可溶性转铁蛋白受体

转铁蛋白受体（TfR）是由两个同源二聚体（180kDa）的亚基通过两条二硫键交联而成的一种II型跨膜糖蛋白,其功能是通过与转铁蛋白（If）的相互作用介导铁的吸收,其表达主要是根据细胞内铁水平进行转录后水平的调节。TfR还在细胞生长和增殖中发挥作用。最近的研究发现TfR在T细胞的激活中发挥了选择性的作用,但是具体的作用还不是完全清楚。可溶性转铁蛋白受体（sTiR）是细胞膜TfR经蛋白酶作用水解生成的分泌到血液中的组织片段,是细胞内Tffi被切断后的单体。是近年来TtR研究的一个新领域,一个新的铁代谢参数,且较稳定,不受炎症性疾病、感染、恶性肿瘤或溶血的影响,其含量与细胞的TIR量呈平行关系。本文就Tffi的结构、表达、功能以及sTiR的测定,参数界定及临床应用进行综述。     

细菌内毒素受体研究新进展

业已明确,内毒素是引起脓毒症的重要致病因子之一,其化学成分脂多糖(LPS)系革兰阴性(G-)菌外膜上的一种双歧性糖脂.许多研究证实,LPS主要成分脂质A与内毒素受体相互作用可激活前炎症细胞因子系统而介导细胞毒反应,最终导致脓毒性休克甚至多器官功能障碍综合征(MODS).临床上一旦出现脓毒性休克,其病死率高达50%以上;据统计,美国每年有10万余人死于此症.因此,深入探讨LPS的分子致病机制,寻求有效的LPS干预途径无疑具有重要意义[1].近年来有关内毒素受体的研究进展迅速,已发现了4类分子家族与LPS脂质A部分结合参与炎症信号转导,包括CD14、巨噬细胞清道夫受体(SR)、Toll样受体(TLRs)和β2白细胞整合素(CD11a/CD18,CD11b/CD18,CD11c/CD18等).目前有关β2白细胞整合素的文献报道较多,现重点对前三者的研究进展进行综述.     

细胞因子受体与哮喘关系研究进展

支气管哮喘特征是炎性介质引起的气道炎症和气道高反应性。多种炎症细胞 ,如淋巴细胞、巨噬细胞、单核细胞、肥大细胞、嗜酸性粒细胞、内皮细胞、血小板等通过炎性介质引起气道上皮损伤、血管渗出、平滑肌痉挛。炎性介质主要通过其本身的受体作用于靶细胞。已经发现多种细胞因子 ,如ＩＬ 2 ,ＩＬ 3 ,ＩＬ 4,ＩＬ 5 ,ＩＬ 6,ＩＬ 9,ＩＬ 10 ,ＩＬ 13 ,ＧＭ ＣＳＦ等在哮喘发病中占有重要地位 ,其受体研究也有较多发现。根据细胞因子的作用方式及功能可将细胞因子分为 :淋巴因子、炎前介质、抑制性细胞因子、生长因子等。而根据其受体功能可将…     

NMDA受体和GABAA受体对未成熟大脑中神经元凋亡的影响

几乎所有哺乳动物未成熟大脑都会经过一个快速发育期，又称之为突触形成期，在此时期短暂的阻滞NMDA受体或过度兴奋GABA-受体都会触发神经元的凋亡。这些触发凋亡的药物有麻醉剂(氯胺酮、氧化亚氮、异氟烷、丙泊酚、氟烷)，抗惊厥剂(苯二氮Zhuo类、巴比妥类)，以及一些被滥用的药物(苯环己哌啶、乙醇、氯胺酮)。人类未成熟大脑的快速发育期从妊娠第6月延续到生后3年。乙醇，既是NMDA受体的拮抗剂又是GABA受体的兴奋剂，可以在快速发育期非常明显的引起广泛的神经元凋亡，乙醇的这种作用可以解释妊娠三期孕妇服用乙醇引起的以脑组织结构改变和神经性行为异常为特征的婴儿乙醇综合征。因此，人们将非常关注在儿科、产科应用的以镇静、麻醉、控制癫痫发作为目的的药物是否会导致未成熟大脑中神经元的大量凋亡。     

雌激素受体和孕激素受体表达与乳腺癌临床病理相关性分析

目的探讨乳腺癌雌激素受体（ER）、孕激素受体（PR）表达及其与乳腺癌各临床病理因素之间的关系。方法收集2011年9月-2012年9月乳腺癌患者105例,用免疫组织化学法检测ER、PR及表皮生长因子受体2（C-erbB-2）并分析其相互关系及与临床各因素之间的关系。结果ER、PR及C-erbB-2的阳性率分别为58．1％、49．5％、59．0％。ER表达与PR表达呈正相关（P〈0．05）,ER、PR表达一致率与C-erbB-2表达呈负相关（P〈0．05）。ER表达与淋巴结转移、组织学分级有相关性（P〈0．05）,与年龄、月经初潮年龄、肿瘤大小、部位、临床分期、病理类型及癌旁组织病理学形态无关。PR表达及ER不同阳性强度表达与临床病理各因素差异均无统计学意义（P〉0．05）。C．erbB．2在有淋巴结转移组中阳性表达率高于淋巴结未转移组（P〈0．05）。结论ER、PR在乳腺癌发生、发展中发挥着重要作用,联合检测ER、PR对评估乳腺癌患者内分泌治疗效果及预后有重要意义。     

凝血酶受体研究进展

凝血酶作为一种丝氨酸蛋白酶，不仅在凝血瀑布反应中发挥作用，而且能够和包括神经细胞在内的多种细胞发生反应，并影响其行为，Ⅱａ如此广泛的生理效应大部分由凝血酶受体介导。越来越多的证据表明，有新的受体参与介导凝血酶的功能。本文综述了已克隆的凝血酶受体的功能，并对可能存在的新的凝血酶受体作一初步探讨。     

G-protein-coupled receptor dimerization: modulation of receptor function

G-protein-coupled receptors (GPCRs) comprise the largest family of transmembrane receptors in the human genome that respond to a plethora of signals, including neurotransmitters, peptide hormones, and odorants, to name a few. They couple to second messenger signaling cascade mechanisms via heterotrimeric G-proteins. Recently, many studies have revealed that GPCRs exist as dimers, which may be present as homo- or heterodimers/oligomers. These recent findings have been met with skepticism, since they are contradictory to the dogma that GPCRs function as monomers. Although the existence of GPCR dimers/oligomers was predicted from early pharmacological and biochemical studies, further studies to critically evaluate this phenomenon were impeded by the lack of appropriate reagents. The availability of cDNAs for GPCRs, of highly selective ligands and of antibodies for these receptors has made it possible to visualize and investigate the functional effects of GPCR oligomers. Pharmacological studies, along with biochemical techniques, such as cross-linking and immunoprecipitation with differentially epitope-tagged receptors, have been employed to demonstrate the oligomerization of a number of GPCRs. Moreover, recent biophysical techniques, such as bioluminescence and fluorescence resonance energy transfer, now make it possible to examine GPCR dimerization/oligomerization in living cells. In this review, we provide a brief overview of some of the techniques employed to describe GPCR dimers, and we discuss their respective limitations. We also examine the implications of dimerization/oligomerization on GPCR function. In addition, we discuss domains of the receptors that are thought to facilitate dimerization/oligomerization. Finally, we consider recent evidence for the subcellular localization of the dimer/oligomer assembly.     

Neurokinin-1 receptor resensitization precedes receptor recycling

Following agonist binding, neurokinin-1 receptors undergo rapid desensitization followed by internalization and recycling. Desensitization requires receptor phosphorylation but does not require internalization, whereas resensitization is thought to require internalization and recycling. Our previous data, however, have suggested that, following activation and desensitization, the return of responsiveness to the neurokinin-1 agonist substance P (termed "resensitization") occurs hours before internalized receptors are recycled back to the plasma membrane. To further investigate this novel mechanism of neurokinin-1 receptor resensitization, we have studied the time courses of neurokinin-1 receptor responsiveness, recycling, and dephosphorylation by measuring cellular Ca(2+) responses, ligand-receptor binding, and receptor phosphorylation, respectively. Concentration-response curves and competition binding curves were obtained at various times following desensitization. The effects of the nonhydrolyzable GTP analog Gpp(NH)p on substance P binding were also studied to assess receptor-G protein coupling. After receptor activation and desensitization, Ca(2+) signaling in response to substance P occurred within 90 min, whereas the return of receptor binding required 240 min. Receptor dephosphorylation was greater than 90% complete 20 min after agonist washout. In addition, the return of substance P responsiveness coincided with a return in sensitivity of substance P binding to Gpp(NH)p, indicating a return in receptor-G protein coupling. These data show that the resensitization of responsiveness to substance P precedes receptor recycling. This may result from a conversion of nonfunctional neurokinin-1 receptors to functional receptors at the plasma membrane.     

ER、PR和LR在子宫内膜癌中的表达及其意义

目的:通过对瘦素受体(LR)和雌、孕激素受体(ER、PR)表达水平的检测分析,探讨它们的表达水平与子宫内膜癌发生、发展的关系以及作为预测内膜癌预后的指标的价值。方法:对66例子宫内膜癌患者手术标本常规进行病理检查,采用免疫组化SP技术研究不同病理分期和组织分级的内膜癌组织中LR与ER、PR的表达情况。结果:子宫内膜癌组织ER、PR及LR阳性率随分期和分级变化较大,子宫内膜上ER、PR的阳性表达随着分期(rs=-0.576,rs=-0.523,P<0.01)和组织分化级别(rs=-0.567,P<0.01;rs=-0.673,P=0.000)的增高而降低,分别呈负相关关系。LR的阳性表达随着分期和组织分化级别的增高而增强,分别呈正相关关系(rs=0.503,P<0.01;rs=0.441,P<0.05)。结论:子宫内膜癌ER、PR、LR阳性表达与病理分期、分化程度有关;对子宫内膜癌内膜组织的LR、ER、PR的联合检测可以提高预测子宫内膜癌预后的准确率。     

The role of receptor structure in determining adenosine receptor activity

Adenosine produces a wide variety of physiological effects through the activation of cell surface adenosine receptors (ARs). ARs are members of the G-protein-coupled receptor family, and currently, four subtypes, the A1AR, A2AAR, A2BAR, and A3AR, are recognized. This review focuses on the role of receptor structure in governing various facets of AR activity. Ligand-binding properties of ARs are primarily dictated by amino acids in the transmembrane domains of the receptors, although a role for extracellular domains of certain ARs has been suggested. Studies have identified certain amino acids conserved amongst AR subtypes that are critical for ligand recognition, as well as additional residues that may differentiate between agonist and antagonist ligands. Receptor regions responsible for activation of Gs have been identified for the A2AAR. The location of these intracellular sites is consistent with findings described for other G-protein-coupled receptors. Site-directed mutagenesis has been employed to analyze the structural basis for the differences in the kinetics of the desensitization response displayed by various AR subtypes. For the A2AAR and A3AR, agonist-stimulated phosphorylation of the AR, presumably via a G-protein receptor kinase, has been shown to occur. For these AR subtypes, intracellular regions or individual amino acids that may be targets for this phosphorylation have been identified. Finally, the role of A1AR gene structure in regulating the expression of this AR subtype is reviewed.     

Inhibition of interleukin 7 receptor signaling by antigen receptor assembly

After the productive rearrangement of immunoglobulin (Ig) heavy chain genes, precursor (pre-)B lymphocytes undergo a limited number of cell divisions in response to interleukin (IL)-7. Here, we present evidence that this phase of IL-7-dependent expansion is constrained by an inhibitory signal initiated by antigen receptor assembly. A line of pre-B cells from normal murine bone marrow that expresses a mu heavy chain with a D-proximal V(H)7183.2 region divides continuously in IL-7. IL-7 responsiveness ceases upon differentiation to the mu(1), kappa(1) stage, despite continuing expression of the IL-7 receptor (IL-7R), suggesting that antigen receptor assembly inhibits IL-7 responsiveness. This is confirmed by introduction of a rearranged lambda light chain gene, which inhibits proliferative signaling through the IL-7R. Inhibition is specific to the IL-7R, because it is overcome by replacement of the IL-7R cytoplasmic domain with corresponding sequences from the closely related IL-2Rbeta chain. Alteration of a single tyrosine residue, Tyr410, in the IL-7R cytoplasmic domain to phenylalanine also prevents the inhibition of proliferation after antigen receptor assembly. Thus, the loss of IL-7 responsiveness after antigen receptor assembly may be mediated through the recruitment of an inhibitory molecule to this residue. Our findings identify a novel mechanism that limits cytokine-dependent proliferation during B lymphopoiesis. This mechanism may be essential for the proper regulation of peripheral B lymphocyte numbers.     

脑膜瘤中三种性激素受体的表达及其意义

目的:探讨脑膜瘤中雄激素受体(AR)、孕激素受体(PR)和雌激素受体(ER)的表达及其意义。方法:运用免疫组织化学及组织微阵列方法,对62例脑膜瘤进行分析研究,免疫组织化学采用En-Vision二步法,一抗选用抗AR、PR、ER单克隆抗体。结果:62例脑膜瘤中PR的阳性率为41.9%,脑膜上皮型、过渡型、纤维型、非典型型及间变型脑膜瘤中PR的阳性率分别为81.8%、55.6%(5/9)、30.8%、33.3%(2/6)和00/0;PR的表达与性别无关,62例脑膜瘤中未发现AR、ER的表达。结论:脑膜瘤中存在较高比例的PR表达,未检测到AR、ER的表达,常规检测脑膜瘤中性激素受体的表达,对脑膜瘤术后的抗性激素受体药物治疗具有指导意义。