黄芩甙对大鼠培养脑切片上谷氨酸递质释放的影响

为研究黄芩甙对谷氨酸（Glu)递质释放的抑制效应，采用15只大白鼠分区切片进行体外培养，加入黄芩甙，观察其对由去极化试剂K^ 引起Glu递质释放的抑制效应，并对这种抑制效应进行了定量分析，结果表明，黄芩甙对Glu释放产生明显的抑制效应。     

Side reactions in solid-phase peptide synthesis and their applications

Side reactions in peptide synthesis indicate steps needing improvement as well as opportunities for structural diversification in combinatorial design. Among the side reactions observed in this study, transesterification of Boc-Glu(OBzl) occurred in TMAH-catalyzed resin attachment, leading to Boc-DKKREE(OMe) in solid-phase synthesis of Boc-DKKREE. Acetylation of Boc-Arg(NO₂)-resin occurred during resin capping with Ac₂O/Et₃N, leading to GPR(Ac) in GPR synthesis. His- and Lys-modification occurred during GHRPLDKKREE cleavage from resin by Pd(OAc)₂-catalyzed hydrogenation in DMF. To verify these side reactions, model experiments were performed, which indicated rapid transesterification of Boc-Glu(OBz1) in methyl. isopropyl, or tert-butyl alcohol into the corresponding ester by TMAH, but not by Cs. This TMAH ability was used to devise a convenient procedure for peptide cleavage. TLC studies of acetylation showed that both Boc-Arg(NO₂) and Boc-Arg(Tos) were stable to Ac-Im treatment, but were modified by Ac₂O/Et₃N. Since transfer hydrogenation of Boc-His(Bzl) and Boc-Lys(Z) in HCOOH or ammonium formate did not generate the formylated side-products of catalytic hydrogenation, DMF and not its decomposed product, HCOOH, appeared involved in side-chain modification. Elimination of the side reactions, by using Cs-derived Boc-Glu(OBzl)-resin for peptide synthesis and catalytic hydrogenation in NMP-HOPr for peptide cleavage. increased the GHRPLDKKREE yield by 1/3. On the other hand, the side reactions provided modified peptides, whose bioassays revealed different importance of the modified side-chains. © Munksgaard 1996.     

谷氨酸对伏隔核痛反应神经元放电的影响

目的：研究脑室内注入谷氨酸（Glu)对伏隔核（NAcc)痛反应神经元放电的影响。方法：细胞外记录神经元放电。结果：（1）伤害性刺激可使NAcc内痛兴奋神经元（PEN）电活动增加，使痛抑制神经元（PIN）电活动减少。（2）脑室内注入Glu可命名NAcc内PEN诱发放电频率增加，潜伏期缩短；使PIN诱发放电频率减少，抑制时程延长。结论：脑室注入Glu可使NAcc内痛反应神经元对伤害性刺激的反应加强，表现出Glu易化疼痛效应。     

外源性谷氨酸对豚鼠耳蜗复合动作电位及微音电位的影响

为观察和研究灌流外源性谷氨酸时复合动作电位（CAP）和微音电位（CM）的变化特点，行全耳蜗灌流不同浓度谷氨酸（1、5、10mmol/2）2h，由圆窗记录CAP和CM。结果显示：CAP的阈值变化与谷氨酸的灌流浓度有剂量依赖关系，灌流谷氨酸可以明显影响CAP的幅阈值，但对CM度及输入输出曲线的非线性特点没有显著的影响。研究表明谷氨酸对内毛细胞有选择性的作用，而对外毛细胞无明显作用。     

Cultured astrocytes express proteins involved in vesicular glutamate release

Bradykinin induces receptor-mediated calcium-dependent release of glutamate from cultured astrocytes through a mechanism that is neither due to cell-swelling mechanism nor due to the reversal of the glutamate transporter. Astrocytes may thus release glutamate using a mechanism resembling the neuronal vesicular release of neurotransmitters. Synaptobrevin is a vesicular protein that together with plasma membrane proteins syntaxin and SNAP-25 participate in formation of the anchoring core complex required for initiation of exocytosis. Here, we demonstrate that synaptobrevin II is present in cultured astrocytes. Furthermore, we demonstrate that botulinus toxin type B and tetanus toxin cause a decrease in synaptobrevin II immunoreactivity and abolish bradykinin-induced release of glutamate from cultured astrocytes. While we were not able to demonstrate the presence of SNAP-25 or syntaxin immunoreactivity in cultured astrocytes, pretreatment with BoTx-A (which cleaves SNAP-25) and BoTx-C (which cleaves syntaxins) result in a decrease in the baseline release of glutamate and diminish the bradykinin-evoked release of glutamate from cultured astrocytes. These findings strongly support the notion that astrocytes may release neurotransmitters using a mechanism similar to the neuronal secretory process.     

In vivo monitoring of extracellular noradrenaline and glutamate from rat brain cortex with 2-min microdialysis sampling using capillary electrophoresis with laser-induced fluorescence detection

The measurement of neurotransmitters by capillary electrophoresis (CE) has emerged as a reliable and sensitive method for microdialysis sample analysis. This paper describes a method which employs laser-induced fluorescence detection (LIFD) of catecholamines and excitatory amino acid derivatives formed after reaction with naphthalene-2,3-dicarboxaldehyde. On-line derivatization of very small volumes of microdialysis samples (500 nl) is developed before two off-line analyses (total run time of less than 10 min) are performed to detect derivatives of catecholamines and excitatory amino acids formed in each sample. High microdialysis temporal resolution is reached (2-min fractions) for the simultaneous monitoring of noradrenaline (NA) and glutamate concentrations from rat brain cortex microdialysates. The system performance is evaluated and pharmacological characterization of the determination of NA in cortical dialysates by CE-LIFD is reported.     

Accumulation of a commercial polychlorinated biphenyl mixture (Aroclor 1016) in adult rhesus monkeys and their nursing infants

Female rhesus monkeys (24) were divided into 3 groups and fed diets calculated to contain 1.0, 0.25 or 0 parts per million (ppm) of a commercial mixture of polychlorinated biphenyls (PCBs), Aroclor 1016. The animals consumed a calculated total of 18.1 +/- 3.1, 4.5 +/- 0.6 and 0 mg Aroclor 1016/kg of body weight over the 87 +/- 9 week experimental period. All animals were bred, conceived and experienced uncomplicated pregnancies. The birth weights of the infants born to females receiving the 1.0 ppm PCB diets were significantly less than those of the control infants. There was a positive relationship between the levels of Aroclor 1016 in the tissues and the dose administered in the diets. Aroclor 1016 content of infant tissues was consistent with maternal adipose tissue PCB levels. The content of Aroclor 1016 in the milk fat of the animals more closely approximated that in the individual's adipose tissue than in the serum. At weaning, the mesenteric fat of the experimental infants contained concentrations of Aroclor 1016 which were 4-7 times that found in the mothers. Analyses of the tissues and fluids of the experimental animals demonstrated accumulation of PCB isomerides. The number of isomerides present and the ratio of those detected differed between adult and infants as well as between milk and serum. After weaning, the pattern of Aroclor 1016 isomerides present in the infants' adipose was similar to that observed at weaning although the concentrations had decreased.     

Disturbed GABAergic transmission in mutant Han-Wistar rats: Further evidence for basal ganglia dysfunction

A mutant strain of Wistar rats which carries an autosomal gene defect is characterized by a progressively developing hyperexcitability, tremor, olfactory and gustatory movements, bradykinesia, ataxia and a pathologically increased muscle tone of hindlimbs which can be measured by recording tonic activity in the electromyogram (EMG) of the gastrocnemius-soleus muscle. The activity of the GABA synthesizing enzyme glutamic acid decarboxylase (GAD) and the receptor binding of GABA as estimated by [3H]GABA binding to synaptic membranes were examined in olfactory bulbs, frontal cerebral cortex, corpus striatum, hippocampus, thalamus, hypothalamus, tectum, substantia nigra, medulla oblongata, cerebellum, and pons of mutant rats. Mutant rats exhibit a lower activity of GAD in synaptosomal fractions of olfactory bulbs and substantia nigra whereas GAD activity within the pons was increased. The changes in the activity of GAD were accompanied by alterations in [3H]GABA binding to synaptic membranes: GABA binding was significantly elevated in the olfactory bulbs and the substantia nigra, but it was markedly reduced in the pons. The functional importance of impaired nigral GABAergic transmission in mutant rats was demonstrated by the fact that intranigral injection of the GABA agonist muscimol reduced the tonic extension of the hindlimbs as indicated by reduced tonic EMG activity of the gastrocnemius-soleus muscle, while intranigral injection of the GABA antagonist bicuculline increased the disturbance.