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排序方式: 共有96条查询结果,搜索用时 15 毫秒
1.
Effects of menstrual cycle on metabolic responses to exercise 总被引:1,自引:0,他引:1
2.
Differential Degradation of Different Benzodiazepine Binding Proteins by Incubation of Membranes from Cerebellum or Hippocampus with Trypsin 总被引:8,自引:7,他引:1
When rat brain membranes were incubated with [3H]flunitrazepam in the presence of UV light, predominantly one protein (P51) was irreversibly labeled in cerebellum and at least two proteins (P51 and P55) were labeled in hippocampus. On digestion of membranes with increasing concentrations of trypsin up to 40% of radioactivity irreversibly bound to proteins was removed from the membranes. In addition, P51 was nearly completely degraded to a peptide with apparent molecular weight 39,000 and this peptide was further degraded to a peptide with apparent molecular weight 25,000. In contrast, protein P55 was only partially degraded by trypsin and yielded two proteolytic peptides with apparent molecular weights 42,000 and 45,000 which seemed to be rather stable against further attack by trypsin. Membranes treated with trypsin still had the capacity to bind [3H]-flunitrazepam reversibly with an affinity similar to that of membranes not previously treated with trypsin. When these membranes were irradiated with UV light, the same proteolytic peptides were detected as in membranes first photolabeled and then digested with trypsin. These results suggest a close association between reversible and irreversible benzodiazepine binding sites and indicate that membrane-associated proteins P51 and P55 are differentially protected against degradation by trypsin. 相似文献
3.
Sieghart Sopper Susanne Hemm Jürgen Meixensberger Cheik Coulibaly Christiane Stahl-Hennig Gerhard Hunsmann Bernhard Fleckenstein Volker ter Meulen Rüdiger Drries 《Journal of medical primatology》1993,22(2-3):138-146
Paired sera and CSF samples were collected from SIVmac-infected macaques. Animals infected with SIVmac251 maintained low gag and high env-specific antibody levels in plasma. Increasing env-specific antibody titers in CSF were associated in one animal with strong intrathecal synthesis. SIVmac239-infected monkeys revealed high antibody titers of gag and env-specificity, in one animal accompanied by weak intrathecal synthesis of virus-specific antibodies. In all animals, the CD4/CD8 ratio in CSF decreased faster compared to blood. 相似文献
4.
Werner Sieghart Chike Item rea Buchstaller Karoline Fuchs Harald Höger Dieter Adamiker 《Journal of neurochemistry》1993,60(1):93-98
Abstract: Polyclonal antibodies were raised to synthetic peptides having amino acid sequences corresponding with the N- or C-terminal part of the γ-aminobutyric acidA (GABAA ) receptor α5 -subunit. These anti-peptide α5 (2–10) or anti-peptide α5 (427–433) antibodies reacted specifically with GABAA receptors purified from the brains of 5–10-day-old rats in an enzyme-linked immunosorbent assay and were able to dose-dependently immunoprecipitate up to 6.3 or 13.1% of the GABAA receptors present in the incubation, respectively. In immunoblots, each of these antibodies reacted with the same two protein bands with apparent molecular mass of 53 or 57 kDa. After exhaustive treatment of purified GABAA receptors with N -Glycanase, each of these antibodies identified two proteins with apparent molecular masses of 46 and 48 kDa. Additional treatment of GABAA receptors with neuraminidase and O -Glycanase resulted in an apparently single protein with molecular mass of 47 kDa, which again was identified by both the anti-peptide α5 (2–10) and the anti-peptide α5 (427–433) antibody. These results indicate the existence of at least two different α5 -sub-units of the GABAA receptor that differ in their carbohydrate content. In contrast to other α- or β-subunits of GABAA receptors so far investigated, at least one of these two α5 -subunits contains O-linked carbohydrates. 相似文献
5.
6.
The release of previously accumulated [3H]taurine and [14C]GABA from crude synaptosomal (P2) fractions isolated from rat cerebral cortex was studied using a superfusion system. The spontaneous efflux of [3H]taurine and [14C]GABA was stimulated by elevated concentrations of K+ (15–133 mM) in a concentration-dependent manner. This K+-stimulated release of [14C]GABA but not of [3H]taurine was enhanced in the presence of Ca2+. However, addition of 3 mM Ca2+ to the superfusion medium in the presence of the ionophore A 23187 resulted in a stimulation of the release of both [3H]taurine and [14C]GABA. These results are discussed in connection with the cellular localization of tourine in the central nervous system. 相似文献
7.
Ojas A. Namjoshi Zhi-jian Wang Sundari K. Rallapalli Edward Merle Johnson Yun-Teng Johnson Hanna Ng Joachim Ramerstorfer Zdravko Varagic Werner Sieghart Samarpan Majumder Bryan L. Roth James K. Rowlett James M. Cook 《Bioorganic & medicinal chemistry》2013,21(1):93-101
Selective modulation of specific benzodiazepine receptor (BzR) gamma amino butyric acid-A (GABAA) receptor ion channels has been identified as an important method for separating out the variety of pharmacological effects elicited by BzR-related drugs. Importantly, it has been demonstrated that both α2β(2/3)γ2 (α2BzR) and α3BzR (and/or α2/α3) BzR subtype selective ligands exhibit anxiolytic effects with little or no sedation. Previously we have identified several such ligands; however, three of our parent ligands exhibited significant metabolic liability in rodents in the form of a labile ester group. Here eight analogs are reported which were designed to circumvent this liability by utilizing a rational replacement of the ester moiety based on medicinal chemistry precedents. In a metabolic stability study using human liver microsomes, four compounds were found to undergo slower metabolic transformation, as compared to their corresponding ester analogs. These compounds were also evaluated in in vitro efficacy assays. Additionally, bioisostere 11 was evaluated in a rodent model of anxiety. It exhibited anxiolytic activity at doses of 10 and 100 mg/kg and was devoid of sedative properties. 相似文献
8.
In cerebellum, 13 different GABA(A) receptor subunits are expressed. The number of different receptor subtypes formed in this tissue, their subunit composition and their quantitative importance so far has not been determined. In the present study, immunodepletion by immunoaffinity chromatography, as well as immunoprecipitation and western blot analysis was performed using 13 different subunit-specific antibodies to provide an overview on the subunit composition and abundance of GABA(A) receptor subtypes in mouse and rat cerebellum. Results obtained indicate that alpha1betaxgamma2, alpha1alpha6betaxgamma2, alpha6betaxgamma2, alpha6betaxdelta and alpha1alpha6betaxdelta are the major GABA(A) receptor subtypes present in the cerebellum. In addition, small amounts of alpha1betaxdelta receptors and a series of minor receptor subtypes containing alpha2, alpha3, alpha4, alpha5, gamma1 or gamma3 subunits are also present in the cerebellum. Whereas the abundance of alpha1alpha6betaxgamma2, alpha6betaxdelta and alpha1alpha6betaxdelta receptors is different in mouse and rat cerebellum, that of other receptors is quite similar in these tissues. Data obtained for the first time provide an overview on the GABA(A) receptor subtypes present in the cerebellum and represent the basis for further studies investigating changes in receptor expression and composition under pathological conditions. 相似文献
9.
Razet R Thomet U Furtmüller R Jursky F Sigel E Sieghart W Dodd RH 《Bioorganic & medicinal chemistry letters》2000,10(22):2579-2583
Analogues of bicuculline devoid of the benzo ring fused to the lactone moiety were prepared by reacting 2-(tert-butyl-dimethylsiloxy)furans with 3,4-dihydroisoquinolinium salts. Some of these compounds (e.g., ROD185, 8) acted as modulators of the GABAA receptor, displacing ligands of the benzodiazepine binding site. They also strongly stimulated GABA currents mediated by recombinant GABA(A) receptors expressed in Xenopus oocytes. 相似文献
10.
Halbach A Nierwetberg D Müller JG Sauer U Kerkau T Stolte N Hofmann P Czub S ter Meulen V Sopper S 《Journal of medical primatology》2000,29(3-4):148-157
Human immunodeficiency virus (HIV) infection leads to a decline of CD4+ T-cells in blood. Because blood represents only a small proportion of the total lymphocyte pool, it is important to investigate other lymphoid organs. So far, only relative proportions of lymphocyte subsets in single peripheral lymph node (LN) regions of HIV-infected patients and simian immunodeficiency virus (SIV)-infected macaques have been documented. We have therefore quantified the absolute numbers of lymphocyte subsets in blood and six different LN regions of 10 uninfected and 26 SIV-infected macaques. In addition, we have determined the expression of markers of activation and differentiation. Already, in uninfected monkeys, there were significant differences in the cellular composition of different LN regions. Infection with SIV resulted in drastic changes in the proportion as well as absolute numbers of different lymphocyte subsets. Moreover, the relative contribution of the single LN regions to the total lymphocyte pool was also altered. 相似文献