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991.
谷氨酸载体在中枢神经系统中的作用 总被引:3,自引:0,他引:3
自1992 年以来,随着各亚型谷氨酸载体氨基酸顺序逐渐被阐明,有关它们在中枢神经系统中的作用研究越来越深入,本文就谷氨酸载体的分布和结构、耦联的离子流、在中枢神经系统发育中的表达变化以及它们的生理作用和病理意义等几方面作一介绍 相似文献
992.
Paul D. Acton Steven A. Kushner Mei-Ping Kung P. David Mozley Karl Plössl Hank F. Kung 《European journal of nuclear medicine and molecular imaging》1999,26(5):518-526
Accurate quantification of neuroreceptors requires full kinetic modeling of the dynamic single-photon emission tomography
(SPET) or positron emission tomography (PET) images, with highly invasive arterial blood sampling. This study investigated
the application of a reference region kinetic model to the dynamics of [99mTc]TRODAT-1 in nonhuman primates, obviating the need for blood sampling. A series of dynamic SPET scans were performed on
two baboons following the injection of approximately 700 MBq of [99mTc]TRODAT-1. Rapid arterial blood samples were taken automatically during scanning. Reconstructed SPET images were co-registered
with magnetic resonance imaging (MRI) scans of the baboons, and regions of interest (ROIs) placed on the striatum, cerebellum
and cerebral hemispheres. The ROI data were combined with metabolite-corrected blood data, and fitted to a three-compartment
kinetic model using nonlinear least squares techniques. The same data were also used in a simplified reference region model,
in which the input function was derived from the nondisplaceable tissue compartment. In addition, semiquantitative blinded
analysis was performed by three raters to determine the point of transient equilibrium in the specific binding curves. All
methods generated values for the ratio of the kinetic rate constants k
3
/k
4, which gives an estimate of the binding potential, BP. These were compared with the full kinetic model. The mean values of
k
3
/k
4 for the three different analysis techniques for each baboon were: 1.17±0.21 and 1.12±0.13 (full kinetic model), 0.93±0.13
and 0.90±0.07 (reference region model), and 0.97±0.18 and 0.92±0.08 (equilibrium method). The reference region method gave
significantly lower results than the full kinetic model (P = 0.01), but it also produced a much smaller spread and better quality fits to the kinetic data. The reference region model
results for k
3
/k
4 correlated very strongly with the full kinetic analysis (r
2 = 0.992, P<0.001), and with the equilibrium model (r
2 = 0.88, P = 0.002). The subjectivity inherent in the equilibrium method produces inferior results compared with both kinetic analyses.
It is suggested that the self-consistency of the reference region model, which requires no arterial blood sampling, provides
a more precise and reliable estimate of the binding of [99mTc]TRODAT-1 to dopamine transporters than full kinetic modeling. The reference region method is also better suited to a routine
clinical environment, and would be able to distinguish smaller differences in dopaminergic function between patient groups.
Received 26 October 1998 and in revised form 11 January 1999 相似文献
993.
Stefan H. J. Dresel Mei-Ping T. Kung XiaoFeng Huang Karl Plössl Catherine Hou Chyng Y. Shiue Joel Karp Hank F. Kung 《European journal of nuclear medicine and molecular imaging》1999,26(4):342-347
[99mTc]TRODAT-1 was the first 99mTc-labeled imaging agent to show specific binding to dopamine transporters (DAT) in the striatum (STR) of human brain. Additionally,
in vitro binding and autoradiographic experiments demonstrated that this tracer also binds to serotonin transporters (SERT)
in the midbrain/hypothalamus (MB) area. In this study, [99mTc]TRODAT-1 was investigated as a potentially useful ligand to image SERT in the MB of living brain. A total of eight single-photon
emission tomography (SPET) scans were performed in two baboons (Papio anubis) after intravenous (i.v.) injection of 740 MBq (20 mCi) of [99mTc]TRODAT-1 using a triple-head gamma camera equipped with ultra-high-resolution fan-beam collimators (scan time: 0–210 min).
In four blocking studies, baboons were pretreated with (+)McN5652 (1 mg/kg, i.v.) or methylphenidate (1 mg/kg, i.v.) to specifically
block SERT or DAT, respectively. After co-registration with magnetic resonance images of the same baboon, a region of interest
analysis was performed using predefined templates to calculate specific uptake in the midbrain area and the striatum, with
the cerebellum as the background region [(MB–CB)/CB, (STR–CB)/CB]. Additionally, two PET scans of the same baboons were performed
after i.v. injections of 74–111 MBq (2–3 mCi) of [11C](+)McN5652 to identify the SERT sites. In [99mTc]TRODAT-1/SPET scans, the SERT sites in the MB region were clearly visualized. Semiquantitative analysis revealed a specific
uptake in MB ([MB–CB]/CB) of 0.30±0.02, which was decreased to 0.040±0.005 after pretreatment with nonradioactive (+)McN5652,
a selective SERT ligand. Pretreatment with methylphenidate reduced the specific binding of [99mTc]TRODAT-1 to DAT sites [(STR-CB)/CB] from 2.45±0.13 to 0.32±0.04 without any effect on its binding to SERT sites [(MB–CB)/CB],
which was confirmed by the co-registration of the [11C](+)McN5652/PET scans. This preliminary study suggests that specific binding of [99mTc]TRODAT-1 to SERT sites can be detected by in vivo SPET imaging despite the low target to background ratio. These findings
provide impetus for further development of similar compounds with improved binding affinity and selectivity to SERT sites.
Received 15 September and in revised form 15 November 1998 相似文献
994.
K. Tokiwa M. Tajima M. Nishina S. Katsura 《International journal of legal medicine》1991,104(3):123-126
Summary Bloodstained threads (1 cm in length) were tested to identify human origin by a direct ELISA-ABC method using biotinylated antibody against human HbA0. By this method human bloodstains were clearly distinguishable from bloodstains of other species including Japanese monkey. The minimum detection lirait of bloodstains prepared from undiluted human whole blood was 1 : 5, 120 (28 ng Hb) and that of bloodstains from diluted human whole blood was 1 : 640 1 : 1, 280. Human Hb was more easily detectable in bloodstains prepared from diluted human blood after extraction with 5% ammonia than after extraction with phosphate-buffered saline. 相似文献
995.
张建亭 《中南大学学报(医学版)》2007,32(4):531-541
ABCG2是半ATP结合盒转运体.它可以转运内源性物质和人工合成的抗肿瘤药物等多种底物.细胞模型和临床研究证明ABCG2的过表达会引起多药耐药.同时,ABCG2的多态性可以影响其功能和肿瘤患者的临床疗效.新近的研究表明ABCG2对于干细胞和肿瘤干细胞有保护作用.因此,ABCG2成为提高化疗耐药肿瘤疗效的理想靶点.本文将综述ABCG2的结构、功能、药理学作用及其对多药耐药和肿瘤干细胞作用的最新进展. 相似文献
996.
Garavito-Aguilar ZV Recio-Pinto E Corrales AV Zhang J Blanck TJ Xu F 《Brain research》2004,1011(2):177-186
In human SH-SY5Y neuroblastoma cells, two distinct intracellular Ca2+ stores, a KCl-/caffeine-sensitive and a carbachol-/IP3-sensitive store, were demonstrated previously. In this study, responses of these two intracellular Ca2+ stores to thapsigargin were characterized. Ca2+-release from these stores was evoked either by high K+ (100 mM KCl) or by 1 mM carbachol, and changes in the intracellular Ca2+ level were monitored using Fura-2 fluorimetry. A sequential stimulation protocol (KCl-->carbachol or vice versa) allowed evaluation of the individual contribution of different Ca2+ stores to the evoked intracellular Ca2+ ([Ca2+]i)-transients and the dynamic interaction between them. Thapsigargin (0.05 nM - 20 microM) alone induced a [Ca2+]i-transient. Both the carbachol- and the KCl-evoked [Ca2+]i-transients were inhibited by thapsigargin, but with very different sensitivities. Thapsigargin inhibited the carbachol-evoked [Ca2+]i-transients with (IC50 = 0.353 nM) or without (IC50 = 0.448 nM) a KCl-prestimulation, but an additional small component, with a much lower sensitivity (IC50=4814 nM), was observed in the absence of a KCl-prestimulation. In contrast, the KCl-evoked [Ca2+]i-transients displayed only one component with a very low sensitivity to thapsigargin in both absence (IC50=3343 nM) and presence (IC50=6858 nM) of a carbachol-prestimulation. These findings suggest that the sarco-/endoplasmic reticular Ca2+ ATPases associated with the KCl-/caffeine- and carbachol-/IP3-sensitive intracellular Ca2+ stores differ from each other, either in types or in their post-translational modification. Such difference might play important role in the regulation of neuronal Ca2+ homeostasis. 相似文献
997.
The increase of Fos expression in the striatum induced by haloperidol, an antagonist of the dopamine D2 receptor, might be related to the activation of glutamatergic neurotransmission, especially that of N-methyl-D-aspartate (NMDA) receptors. In this study, using behavioral and immunohistochemical techniques, we examined the effects of a noncompetitive NMDA antagonist, (+)-MK-801, and an NMDA receptor NR2B subunit antagonist, ifenprodil, on catalepsy, an extrapyramidal symptom; in this context, we also considered the expression of Fos protein in the forebrain after the administration of haloperidol. Catalepsy in mice, induced by the administration of haloperidol (1 mg/kg), was inhibited by pretreatment with (+)-MK-801 (0.2 mg/kg) or ifenprodil (10 mg/kg). Furthermore, pretreatment with (+)-MK-801 (0.2 mg/kg) significantly attenuated the induction of Fos-immunoreactive (IR) cells in the dorsomedial, dorsolateral, and ventrolateral striatum, but not in the shell region of the nucleus accumbens after the administration of haloperidol, whereas pretreatment with ifenprodil (10 mg/kg) significantly attenuated the induction of Fos-IR cells in all of these areas. It is known that ifenprodil binds sigma receptors and alpha-1 adrenergic receptors with high affinity. Pretreatment with the sigma receptor antagonist BD-1407 (3 mg/kg) or the alpha-1 adrenergic receptor antagonist prazosin (3 mg/kg) affected neither catalepsy nor the expression of Fos-IR cells after the administration of haloperidol. However, pretreatment with CP-101,606 (1 mg/kg), a selective antagonist for the NR2B subunit of the NMDA receptor, significantly attenuated catalepsy and the expression of Fos-IR cells in the forebrain after the administration of haloperidol. These results suggest that the NMDA receptor antagonists attenuated the induction of catalepsy and Fos-IR cells in forebrain after the administration of haloperidol. It was also suggested that haloperidol-induced expression of Fos-IR cells in the shell region of the nucleus accumbens might be differentially regulated by NMDA receptor subunits. Therefore, it appears that selective antagonists for the NR2B subunit of the NMDA receptor (e.g., CP-101,606) might be useful drugs for the treatment of extrapyramidal side effects (EPS) associated with the chronic use of typical antipsychotics such as haloperidol. 相似文献
998.
The antiestrogen, tamoxifen (TMX), has been shown to function as a neuroprotectant against the nigrostriatal dopaminergic (NSDA) neurotoxin, methamphetamine (MA), within male mice. In the present report, we examined the effects of a combined infusion of TMX and MA within superfused striatal tissue fragments of male mice as an approach to understand some of the bases for TMX to function as a NSDA neuroprotectant within male mice. In Experiment 1, a coinfusion of TMX at 1, 10, or 100 pg/ml were all equally effective in increasing MA-evoked dopamine (DA) output as compared with a 0 pg/ml (control) dose. In Experiment 2, we tested whether this effect of TMX was specific for MA-evoked DA output by coinfusing TMX with a depolarizing concentration of potassium chloride (K+ -30 mM). No statistically significant differences were obtained between superfusions of striatal tissue fragments stimulated with K+ in the presence or absence of TMX (100 pg/ml). In Experiment 3, we assessed whether these effects of TMX may be exerted upon the dopamine transporter (DAT) by coinfusing DA (1 microM) in the presence or absence of TMX (100 pg/ml). No differences in DA recovery rates were obtained between superfusions performed in the presence or absence of TMX. Taken together, these results show that the striatum of male mice is very sensitive to the modulatory effects of TMX upon MA-evoked DA output. These effects of TMX appear to be relatively specific for MA-evoked DA output, as K+ -stimulated DA was not altered by TMX, and do not appear to exert these effects by altering dopamine transporter function. 相似文献
999.
1. Glutamate transporters (or excitatory amino acid transporters (EAAT)) are responsible for removing synaptically released glutamate from the extracellular space. The failure of EAAT to carry out this role will lead to excessive stimulation of glutamatergic receptors, causing excitotoxicity and cell death. 2. Glutamate is cotransported into the cell with three Na+ and one H+, followed by the counter-transport of one K+. In addition, glutamate and Na+ binding activates an uncoupled chloride conductance. Thus, glutamate transporters can function as both a transporter and an ion channel. At present, there is no clear understanding of the structural basis for the dual functions of glutamate transporters and, in the present review, we shall discuss some recent studies that have started to address this question. 3. It is possible to modulate one function of glutamate transporters without affecting the other, which suggests that the two functions have separate molecular determinants, and a number of models have been suggested to account for the dual functions of the EAAT that predict both single and dual pores for transporter function. 4. It appears that the two functions of glutamate transporters arise from separate transmembrane domains. The C-terminal region of the transporters forms the glutamate translocation domain, whereas the second transmembrane domain in the N-terminal half of the protein plays a crucial role in chloride channel function. Although the two functions arise from separate molecular determinants, the two functional domains are likely to be in close proximity. The significance of these observations will be discussed in terms of likely functional models for the transport and channel processes. 相似文献
1000.
线粒体KATP开放剂二氮嗪促进星形胶质细胞摄取谷氨酸 总被引:4,自引:0,他引:4
目的研究线粒体ATP敏感性钾通道(mitochondrial ATP-sensitive potassium channel, mitoKATP)开放剂二氮嗪(diazoxide)对星形胶质细胞摄取谷氨酸(glutamate)的影响.方法取新生大鼠脑星形胶质细胞作原代培养,用液体闪烁计数仪测定[3H]-D,L-谷氨酸的摄入量判断细胞的谷氨酸摄取功能.结果二氮嗪呈浓度依赖性地促进星形胶质细胞摄取谷氨酸,且能抑制1-甲基-4-苯基吡啶离子(1-methyl-4-phenylpyridinium,MPP+)对星形胶质细胞摄取谷氨酸的损伤作用;浓度在100μmol·L-1以上时,二氮嗪可完全逆转MPP+对星形胶质细胞摄取谷氨酸的抑制作用;二氮嗪的上述作用可被选择性mito KATP 阻断剂5-羟基癸酸 (5-hydroxydecanoate,5-HD)拮抗.结论二氮嗪通过开放mitoKATP增强星形胶质细胞谷氨酸转运体(glutamate transporters, GluTs)的功能. 相似文献