烟碱乙酰胆碱受体及其与新烟碱类相互作用的研究进展

对烟碱乙酰胆碱受体(nAChRs)的结构与功能、配体结合部位、门控机理以及与新烟碱类的相互作用进行了综述,并对nAChRs亚基基因突变和敲除对新烟碱类和多杀菌素敏感性的影响进行了讨论。nAChRs在脊椎动物和昆虫的胆碱能突触的快速神经传递中起着重要作用,其在昆虫中仅存在于中枢神经系统(CNS)中,而在脊椎动物中同时存在于CNS和神经肌肉连接处。nAChRs是新烟碱类杀虫剂、多杀菌素和杀螟丹的作用靶标。肌肉和CNS中的nAChRs是一个由两个α和三个非α(β,γ和δ)亚基组成的异数五聚体,该受体主要有三部分:一个在细胞外发现的区域(胞外区)、一个位于膜内的区域(跨膜区),另一个是位于细胞内的区域(胞质区)。每个亚基(从N-C端)都具有一个包含乙酰胆碱(ACh)结合部位的细胞外结构域;4个跨膜结构域(M1~4),其中M2的大部分氨基酸位于离子通道的内壁;一个胞质噜扑(loop)和一个胞外C端。通道门位于孔道内的疏水区。ACh结合部位位于天然和功能受体的两个亚基的界面,是由一个亚基的3个噜扑(A-C)和另一个亚基的3个噜扑(D-F)构成。每当受体与ACh(或其他激动剂)分子结合时,M2 α螺旋体的构象发生改变,使通道开启,处于阳离子传导状态,直至一个或两个激动剂分子从结合口袋解离,通道才关闭。如果激动剂一直存在,并反复结合,则通道处于脱敏状态。nAChRs与新烟碱类的各种选择性作用取决于新烟碱类的结构以及nAChRs的亚基组成。     

Expression of receptor tyrosine kinases VEGFR-1 (FLT-1), VEGFR-2 (KDR), EGFR-1, PDGFRa and c-Met in canine primary brain tumours

Inhibition of tumour growth and angiogenesis by targeting key growth factor receptors is a promising therapeutic strategy for central nervous system tumours. Characterization of these growth factor receptors in canine primary brain tumours has not been done. Using quantitative real‐time TaqMan polymerase chain reaction (PCR), we evaluated the expression of messenger RNA (mRNA) for five tyrosine kinase growth factor receptors (vascular endothelial growth factor receptor [VEGFR]‐1, VEGFR‐2, endothelial growth factor receptor [EGFR]‐1, platelet‐derived growth factor receptor a [PDGFRa], and c‐Met) relative to normal cerebral cortex in 66 spontaneous canine primary brain tumours. Increased expression of VEGFR‐1 and VEGFR‐2 mRNA was greatest in grade IV astrocytomas (glioblastoma multiforme) and grade III (anaplastic) oligodendrogliomas. EGFR‐1 mRNA expression was more consistently increased than the other receptors in all tumour types, while increased PDGFRa mRNA expression was mostly restricted to oligodendrogliomas. The similarities in increased expression of these tyrosine kinase growth factor receptors in these canine tumours, as compared to data from their human counterparts, suggest that common molecular mechanisms may be present.     

Immunohistochemical expression of progesterone receptors, growth hormone and insulin growth factor-I in feline fibroadenomatous change

The immunohistochemical expression, tissue-specific and cell-specific distribution patterns of progesterone receptors (PR), growth hormone (GH) and insulin growth factor-I (IGF-I) have been studied in 22 cases of feline fibroadenomatous change (FFAC). PR and GH were detected in all cases and were distributed homogeneously throughout the lesion, while IGF-I was detected in 77% of the cases at the site of ductal budding. The simultaneous expression of PR, GH and IGF-I was detected in epithelial cells in 14 of 22 cases while PR and GH expression only was detected in epithelial cells in 11 cases. Cases that expressed GH and IGF-I without PR expression in the stroma were the most numerous. Double immunohistochemical staining showed the co-localisation of PR and GH in a subset of ductal epithelial cells located between basal/myoepithelial and luminal cells (probably undifferentiated stem cells). These results suggest that ligand-activated progesterone receptors may induce the local synthesis of GH which in turn may exert its proliferative action directly and also indirectly through the production of other growth factors, such as IGF-I, in an autocrine/paracrine manner.     

Ontogeny of IGF-I responsiveness to bGH in young lambs

The ontogeny of hepatic growth hormone (GH) receptors (GHR), as measured by responses of both plasma insulin-like growth factor-I (IGF-I) and hepatic GHR to an exogenous bGH stimulus, was examined using sheep of different ages (Days 1-7, 14-21, 28-35, and 56-63 of life, and yearlings). The IGF-I response to bGH was first examined in yearling sheep using two doses of bGH (0.1 and 0.2 mg/kg LW/d). Based on these results, lambs in four groups up to Day 63 of life were treated for 5 d with bGH (n = 10) at a dose of 0.15 mg/kg LW/d or with saline (n = 10). Jugular blood samples were taken once daily on Days - 1, 4, and 5 of treatment. bGH treatment in lambs up to Day 63 of life had little effect on plasma concentrations of GH, insulin, glucose or urea, but significantly (P < 0.05) increased circulating concentrations of IGF-I at all ages and of NEFA at Day 62/63 of life. In contrast, bGH treatment at either dose in yearlings significantly increased these parameters, except for plasma urea concentrations which were decreased in bGH-treated yearlings. However, the responses of plasma IGF-I concentration to bGH stimulus in lambs up to Day 63 of life were small compared to those in yearling sheep. Consistent with this, bGH treatment failed to affect hepatic GH binding in young lambs, but up-regulated it in yearling sheep. Furthermore, basal (unstimulated) GH binding did not differ between sheep of 7 vs. 63 vs. 365 d of age, despite the greater IGF-I responses to bGH in the latter group. It is suggested that hepatic GHR in lambs up to Day 63 of life are not fully functional compared to the situation in yearlings.     

Actions of quinolizidine alkaloids on Periplaneta americana nicotinic acetylcholine receptors

BACKGROUND: Botanical insecticides do not play a major role as crop protectants, but they are beneficial in some applications. The authors investigated the actions of naturally occurring alkaloids on insect nicotinic acetylcholine (ACh) receptors (nAChRs) by evaluating their abilities to inhibit specific binding of [³H]imidacloprid (IMI) to nerve‐cord membranes from Periplaneta americana L. Two alkaloids were also tested for their actions on nAChRs expressed by cockroach neurons using patch‐clamp electrophysiology. RESULTS: Four natural quinolizidine alkaloids (matrine, sophocarpine, cytisine and aloperine) exhibited more than 50% inhibition of [³H]IMI binding at 10 µM , although other compounds were found to have no or low inhibitory activity. The rank order of potency based on concentration–inhibition curves was cytisine > sophocarpine ≥ aloperine ≥ matrine. Patch‐clamp analysis indicated that sophocarpine and aloperine were not agonists of nAChRs expressed in P. americana neurons, yet, at 10 µM , aloperine, but not sophocarpine, suppressed ACh‐induced inward currents significantly. CONCLUSION: Three of the four natural alkaloids tested possess structural moieties that are necessary for interaction with P. americana nAChRs. Aloperine, which possesses a unique structure and showed a distinctive dose–response curve, was found to act as an antagonist. Appropriate modifications of these alkaloids might result in novel insecticidal nAChR ligands. Copyright © 2008 Society of Chemical Industry     

Comparison of steroid receptor expression in normal, dysplastic, and neoplastic canine and feline mammary tissues

Steroid receptor expression was assessed by immunohistochemistry in neoplastic, hyperplastic/dysplastic, and normal mammary tissue samples removed from 68 queens and 47 bitches, using monoclonal antibodies against human oestrogen-alpha (ER) and progesterone receptors (PR). Mammary lesions were classified according to World Health Organization (WHO) criteria, and all animals with invasive carcinomas were clinically followed for 2 years. Stromal and/or lymphatic invasion and histological grading were also recorded. In both species, ER expression was significantly higher in healthy tissues, hyperplastic/dysplastic lesions, and benign tumours than in carcinomas. The loss of ER expression was more marked in feline than in canine carcinomas. In queens, PR expression increased in dysplastic lesions and "in situ" carcinomas and decreased in invasive carcinomas, even if parts of these tumours were still PR-positive. In bitches no significant variation in PR expression was observed between normal tissue, dysplasias, and benign neoplasms, but was significantly lower in carcinomas. In both species ER and PR expression in invasive carcinomas did not correlate either with histological parameters or overall survival time. This study demonstrates several differences in steroid hormone dependency between the two species. The percentage of PR-positive feline carcinomas suggests a possible role of progesterone in promoting early tumour cell growth in queens. The low percentage of ER-positive invasive carcinomas further demonstrated the aggressive phenotype and behaviour of feline mammary tumours.     

狭胸天牛幼虫触角主感器及下颚须和下唇须感受器扫描电镜观察

利用扫描电镜观察了狭胸天牛幼虫触角主感器及其下颚须和下唇须顶端感受器的形态，种 类和分布，并讨论了其结构与功能的关系。结果表明，触角主感器受肾形成唇形，长约９８．０μｍ，宽约２４．５μｍ。下颚须顶端感受器２０个～２５个，下唇须顶端约１５个感受器，根据不同形态，大致分为３种类型；栓锥形，锥柱形和腔锥形。栓锥形和锥柱形感受器分别着生于下颚须和下唇须顶端表面，腔锥形感受器着生于它们的端节侧面。     

口蹄疫流行病学及感染机制的研究进展

口蹄疫(Foot-and-mouth disease FMD)是由口蹄疫病毒(Foot-and-mouth disease virus FMDV)引起偶蹄动物的一种急性、热性、高度接触性传染病。FMDV有多种血清型及其亚型,目前主要引起动物致病的就有7种,即A、O、C、SATⅠ、SATⅡ、SATⅢ和亚洲Ⅰ型(AsiaⅠ型)。病毒通常在细胞受体的参与下才入侵宿主细胞,进行扩增生命循环,感染宿主细胞,使得该病得以广泛流行。但由于口蹄疫病毒的高度变异性和适应性而在流行中出现新的特点,以及被发现的病毒在动物体内和细胞中长期存在而引发FMDV的持续感染等问题,使得本病不能有效被控制而在许多国家和地区重新暴发和流行。为此本文将口蹄疫病原学、流行病学、病毒细胞受体及其病毒在体内持续感染形成的原因方面进行的论述,为口蹄疫病毒感染机制的研究提供了科学的依据。     

大鼠发情周期的子宫组织雌激素受体定位的初步研究

本试验选用 SD 系大鼠,用常规阴道抹片法鉴定发情。采用免疫组织化学的过氧化物酶—抗过氧化物酶复合物(PAP)法,进行雌激素受体(ER)定位。在子宫的内膜固有层、肌层和浆膜层,发现抗雌二醇抗体的免疫反应阳性细胞,而在内膜上皮细胞内无阳性染色。这种阳性染色可以被乙烯酚所阻断,不加抗雌二醇抗体的结果使染色呈阴性。发情周期4个不同时期的子宫组织中免疫反应阳性细胞表现出量的变化,以发情间期为基础,发情前期较多,发情期和发情后期依次减少,其动态变化与前人报道发情周期中雌二醇在血浆中的浓度变化是对应的。并发现发情周期中子宫组织的肥大细胞与雌激素受体的分布和变化有着相似的特点。