蛋白激酶C对大鼠缺血海马突触体谷氨酸摄取的调控作用

采用大鼠海马脑片体外缺血模型,观察海马突触体内蛋白激酶Ｃ（ＰＫＣ）活性的变化,以及这种变化对突触体谷氨酸（ＧＬＵ）摄取的影响。结果显示：海马脑片体外“缺血”１０ｍｉｎ,其突触体内ＰＫＣ活性基本不变,而缺血３０ｍｉｎ,突触体内ＰＫＣ活性显著上升（Ｐ＜０．０１,ｎ＝６）;非Ｎ－甲基－Ｄ－天门冬氨酸（ＮＭＤＡ）受体拮抗剂ＤＮＱＸ有效地抑制ＰＫＣ活性的同时,可降低胞外ＧＬＵ的堆积,而ＮＭＤＡ受体阻断剂ＡＰ＿５无作用。进一步实验证明,ＰＫＣ激动剂ＰＤＢ浓度依赖性地抑制突触体对３Ｈ－ＧＬＵ的摄取（ＩＣ５０＝１３１±１０μｍｏｌ／Ｌ）,此抑制作用可由ＰＫＣ抑制剂Ｈ－７（１００μｍｏｌ／Ｌ）抵消。提示脑缺血诱发ＧＬＵ堆积的作用机理可能是：脑缺血引发钙内流导致ＧＬＵ过量释放,ＧＬＵ又通过突触前非ＮＭＤＡ受体激活ＰＫＣ,抑制其自身摄取,正反馈性加重胞外ＧＬＵ的堆积。     

γ—氨基丁酸（GABA）对离体大鼠卵巢颗粒细胞孕酮分泌的影响

本文观察了ＧＡＢＡ对大鼠分散颗粒细胞生孕酮的影响。结果表明：当ＧＡＢＡ浓度为１０＾－＾６ｍｏｌ／Ｌ时明显促进颗粒细胞基础孕酮分泌（Ｐ＜０．０５）。但更高浓度（１０＾－＾５ｍｏｌ／Ｌ）时则表现抑制ＨＣＧ刺激孕酮生成的效应（Ｐ＜０．０２）。提示颗粒细胞的激素分泌功能可能受到ＧＡＢＡ的调控。     

中国伞滑刃线虫属─新纪录（真滑刃目：寄生滑刃科）

中国伞滑刃线虫属─新纪录（真滑刃目：寄生滑刃科）ＴＨＥＮＥＷＲＥＣＯＲＤＯＦＢＵＲＳＡＰＨＥＬＥＮＣＨＵＳＦＲＯＭＣＨＩＮＡ（ＡＰＨＥＬＥＮＣＨＩＤＡ：ＰＡＲＡＳＩＴＡＰＨＥＬＥＮＣＨＩＤＡＥ）￥ＹＩＮＧａｎ－ｌｉｕ;ＦＡＮＧＹｕ－ｓｈｅｎｇ（Ｄｅｐ...     

乙酰胆碱对大鼠体外抗体生成的影响

目的：观察不同浓度乙酰胆碱（ＡＣｈ,１０－１０～１０－５ｍｏｌ／Ｌ）对大鼠体外抗体生成的影响,并初步探讨其作用机制,从细胞水平了解乙酰胆碱与免疫功能之间的关系。方法：用体外抗体生成的检测方法,用绵羊红细胞（ＳＲＢＣ）刺激大鼠肠系膜淋巴结Ｂ细胞转化成抗体形成细胞（ＡＦＣ）,然后检测其抗体生成量。结果：①１０－１０～１０－７ｍｏｌ／ＬＡＣｈ能显著抑制体外抗体生成,其中１０－８和１０－７ｍｏｌ／ＬＡＣｈ的作用较强,而１０－６和１０－５ｍｏｌ／ＬＡＣｈ无明显的抑制作用;②Ｍ型胆碱能受体激动剂毛果芸香碱（１０－８和１０－７ｍｏｌ／Ｌ）能明显减弱体外抗体生成,而Ｎ型受体激动剂烟碱（１０－８和１０－７ｍｏｌ／Ｌ）没有显著的减弱作用,Ｍ型受体拮抗剂阿托品（１０－７和１０－６ｍｏｌ／Ｌ）可完全阻断ＡＣｈ抑制体外抗体生成的作用;③ＡＣｈ分别在Ｂ细胞用ＳＲＢＣ刺激后３～４８ｈ中的６个不同时间与淋巴细胞作用,其抗体生成仍然是减少的。结论：ＡＣｈ可非浓度依赖性地抑制大鼠的体外抗体生成;此作用可能由Ｂ细胞上的Ｍ型胆碱能受体介导;且ＡＣｈ可能主要影响Ｂ细胞转化的后期过程。     

猕猴桃果实的生理生化特征

猕猴桃果实的生理生化特征魏玉凝,李曜东（中国科学院植物所,北京１０００４４）ＴＨＥＰＨＹＳＩＯＬＯＧＩＣＡＬＡＮＤＢＩＬＣＨＥＭＩＣＡＬＣＨＡＲＩＣＴＥＲＩＳＴＩＣＳＯＦＫＩＷＩＦＲＵＩＴ￥ＷｅｉＹｕ－ｎｉｎｇ;ＬｉＹａｏ－ｄｏｎｇ（Ｉｎｓｔｉｔｕｔ...     

烟草Z诱导株的生长及开花

烟草Ｚ诱导株的生长及开花姚坤林,孟繁静（北京农大生物学院,北京１０００９４）ＧＲＯＷＴＨＡＮＤＦＬＯＷＥＩＮＧＯＦＴＨＥＲＥＧＥＮＥＲＡＴＥＤＰＬＡＮＴＳＩＮＤＵＣＥＤＢＹＺＥＡＲＡＬＥＮＯＮＥ￥ＹａｏＫｕｎ－ｌｉｎ;ＭｅｎｇＦａｎ－Ｊｉｎｇ（Ｃｏｌ...     

乙酰胆碱,谷氨酸与GABA对丘脑腹内侧核神经元活动的影响

本文采用微电泳方法观察到在大鼠丘脑腹内侧核（ＶＭ）,微电泳给予乙酰胆碱（ＡＣＨ）使所有受试神经元自发放电频率加快,谷氨酸（ＧＬＵ）使大多数神经元放电加快,它们的作用依赖于电流强度;而γ氨基丁酸（ＧＡＢＡ）和氯苯氨丁酸则抑制大多数神经元的放电活动,但前者的作用快速而暂短,而后者的作用相对缓慢而持久。在微电泳ＡＣＨ或ＧＬＵ的过程中,给予ＧＡＢＡ可拮抗它们的兴奋作用。双钴碱使大多数神经元的自发放电频率加快,而阿托品和ＭＫ８０１对自发放电的影响较小。这些结果表明ＧＡＢＡ,ＡＣＨ和ＧＬＵ等递质活动在同一ＶＭ神经元有重要的会聚作用;ＧＡＢＡ对ＶＭ神经元有紧张性抑制作用。     

糖皮质激素抑制加压素释放的细胞膜机制

利用离休孵育脑薄片和放射免疫测定其释放的精氨酸加压素（ＡＶＰ）方法,探讨糖皮质激素（ＧＣ）在不能进入细胞内的情况下,对去肾上腺大鼠的下丘脑薄片释放ＡＶＰ的快速影响及其可能的细胞膜机制。结果如下：（１）下丘脑薄片能够稳定地释放ＡＶＰ（２ｈ）,其释放量为１５．４２±１．２８ｐｇ／ｍｉｎ;（２）牛血清白蛋白耦联皮质酮（Ｂ－ＢＳＡ）对ＡＶＰ的释放具有快速的（２０ｍｉｎ）抑制性效应,在１０￣（－７）─１０￣（－４）ｍｏｌ／Ｌ范围内呈剂量一效应关系;（３）ＧＣ细胞内受体拮抗剂ＲＵ４８６（１０￣（－４）─１０￣（－３）ｍｏｌ／Ｌ）能部分地阻断Ｂ─ＢＳＡ的快速抑制效应;（４）孵育液中Ｃａ￣（２＋）程度升高,Ｂ─ＢＳＡ的快速抑制效应明显增强;反之,孵育液中无Ｃａ￣（２＋）则Ｂ－ＢＳＡ的快速抑制效应有所减弱。表明ＧＣ在未进入细胞内的情况下也可快速地抑制大鼠下丘脑薄片释放ＡＶＰ,因此没有通过传统的基因组机制,而是由非基因组机制介导的,其作用部位在细胞膜水平上,可能是影响Ｃａ￣（２＋）的跨细胞膜内流通量或／和影响有Ｃａ￣（２＋）参与的ＡＶＰ释放过程的结果。     

SKF38393抑制大鼠DRG分离神经元GABA-激活电流

在大鼠新鲜分离ＤＲＧ神经元标本上应用全细胞膜片箝记录,观察了多巴胺Ｄ１受体的选择性激动剂ＳＫＦ３８３９３ＨＣＩ对ＧＡＢＡ－激活电流的作用。大部分受检细胞对ＧＡＢＡ敏感,１０＾－６－１０＾－３－ｍｏｌ／Ｌ ＧＡＢＡ可于引起呈剂量依赖性的明显去敏感作用的内向电流。     

汽枪子弹击中右心室及心电图改变一例

汽枪子弹击中右心室及心电图改变一例史训凡，夏斌赞（湖南医科大学湘雅医院－心内科·长沙·４１０００５）ＴＨＥＣＨＡＮＧＥＯＧＥＣＧＡＦＴＥＲＲＩＧＨＴＶＥＮＴＲＩＣＬＥＳＨＯＯＴＥＤＢＹＧＡＳＧＵＮＳｈｉＸｕｎｆａｎ；ＸｉａＢｉｎｚａｎ（Ｄｅｐａｒｔｍ...     

Effects of GABA and GABA receptor inhibition on differentiation of mesencephalic precursors into dopaminergic neurons in vitro

Neurotransmitters have been shown to control CNS neurogenesis, and GABA-mediated signaling is thought to be involved in the regulation of nearly all key developmental stages. Generation of dopaminergic (DA) neurons from stem/precursor cells for cell therapy in Parkinson's disease has become a major focus of research. However, the possible effects of GABA on generation of DA neurons from proliferating neurospheres of mesencephalic precursors have not been studied. In the present study, GABA(A), and GABA(B) receptors were found to be located in DA cells. Treatment of cultures with GABA did not cause significant changes in generation of DA cells from precursors. However, treatment with the GABA(A) receptor antagonist bicuculline (10(-5) M) led to a significant increase in the number DA cells, and treatment with the GABA(B) receptor antagonist CGP 55845 (10(-5) M) to a significant decrease. Simultaneous treatment with bicuculline and CGP 55845 did not induce significant changes. Apoptotic cell death studies and bromodeoxyuridine immunohistochemistry indicated that the aforementioned differences in generation of DA neurons are not due to changes in survival or proliferation of DA cells, but rather to increased or decreased differentiation of mesencephalic precursors towards the DA phenotype. The results suggest that these effects are exerted via GABA receptors located on DA precursors, and are not an indirect consequence of effects on the serotonergic or glial cell population. Administration of GABA(A) receptor antagonists in the differentiation medium may help to obtain higher rates of DA neurons for potential use in cell therapy for Parkinson's disease.     

Dopamine Inhibits Calcium-Independent γ-[3H]Aminobutyric Acid Release Induced by Kainate and High K+ in the Fish Retina

Kainic acid (KA) at micromolar concentrations stimulated the release of gamma-[3H]aminobutyric acid [( 3H]GABA) from a particulate fraction of the carp (Cyprinus carpio) retina. The KA action was dose-dependent but Ca2+-independent. A similar response was elicited by another glutamate receptor agonist, quisqualic acid, and high K+, but not by an aspartate agonist, N-methyl-D-aspartic acid. The stimulatory action of KA on the [3H]GABA release was selectively blocked by the KA blockers gamma-D-glutamylglycine and cis-2,3-piperidine dicarboxylic acid. Dopamine (DA), which is contained in DA interplexiform cells in the carp retina, inhibited the [3H]GABA release induced by KA and high K+ in a dose-dependent manner. 5-Hydroxytryptamine and two well-known GABA antagonists, bicuculline (Bic) and picrotoxin (Pic), also mimicked the DA effect on the GABA release at a comparable concentration. This inhibitory effect of DA as well as Bic and Pic on the [3H]GABA release evoked by KA was clearly antagonized by a DA blocker, haloperidol. The action of these agents (KA, DA, GABA antagonist) belonging to three different receptor categories on the GABAergic neurons (possibly external horizontal cells; H1 cells) is discussed in relation to other electrophysiological studies on the lateral spread of S-potentials between H1 cells.     

Interaction between opiates and hypothalamic dopamine on prolactin release.

Opiate stimulation of prolactin (PRL) release appears to involve a hypothalamic mechanism(s). The present study utilized both central acting drugs and direct measurement of hypothalamic dopamine (DA) to investigate this problem. Administration of L-dopa, the precursor of DA; piribedil, a DA agonist; or amineptine, a DA reuptake inhibitor, each decreased serum PRL concentrations. Morphine sulfate (MS) and haloperidol (HAL) significantly increased serum PRL levels. L-dopa and piribedil reversed the stimulatory effect of MS on serum PRL concentrations by increasing dopamine activity. MS blocked the inhibitory effects of amineptine on serum PRL release, possibly by decreasing the concentration of DA available for reuptake. Injection of subeffective doses of HAL concurrently with a subeffective dose of MS increased serum PRL concentrations, by an additive inhibitory action on dopaminergic activity. β-endorphin, an endogenous opioid peptide, decreased the rate of DA turnover in the median eminence, and increased serum PRL levels approximately 10 - fold. These observations indicate that opiates stimulate PRL release by decreasing DA activity in the median eminence.     

GABAergic Inhibition on Dopamine Cells of the Fish Retina: A [3H]Dopamine Release Study with Isolated Cell Fractions

Inner retinal cells including dopamine (DA) cells were isolated and fractionated from the carp (Cyprinus carpio) retina by an enzyme cell dissociation and metrizamide gradient centrifugation method. When gamma-aminobutyric acid (GABA) antagonists (bicuculline and picrotoxin) were added into the perfusate over such a cell fraction, they stimulated the release of [3H]DA which had been preloaded in the cell fraction. The action of GABA antagonists was dose and Ca2+ dependent. Their minimal effective concentration was very low (0.5 microM). A similar action was elicited by high K+. In the presence of excess GABA, this stimulatory action of GABA antagonists and high K+ on [3H]DA release was completely abolished. To interpret the action of GABA antagonists on DA cells, isolated cell fractions were preincubated with GABAse. After such a treatment, the stimulatory effects of GABA antagonists and high K+ on [3H]DA release were differentiated from each other; the former disappeared whereas the latter remained unchanged. The data strongly suggest that GABA inhibits the DA release from retinal DA cells and thus the GABA antagonists affect [3H]DA release from cell fractions not by a direct membrane action but by a disinhibition mechanism via GABA receptors on the DA cell bodies.     

Modulation of a neuronal network by electrical high frequency stimulation in striatal slices of the rat in vitro

The effects of the GABA(A) receptor antagonist bicuculline, the D2-like receptor antagonist sulpiride and the D1-like receptor antagonist SCH-23390 on the electrical high frequency stimulation (HFS)-evoked gamma-aminobutyric acid (GABA) and dopamine (DA) release were measured from slices of the rat striatum by means of HPLC method with electrochemical detection. HFS with 130Hz stimulated veratridine-activated GABAergic neurons resulting in an increased GABA outflow while DA outflow decreased. In the presence of the GABA(A) receptor antagonist bicuculline extracellular GABA and DA outflow were enhanced. When the competitive dopamine D2-like receptor antagonist S-(-)-sulpiride was added to incubation medium, the HFS-evoked stimulatory effect on GABA outflow declined to values found after veratridine (1microM) without HFS. After co-incubation of sulpiride and the competitive D1-like receptor antagonist R-(+)-SCH-23390, the effect of sulpiride on HFS plus veratridine-evoked GABA outflow was completely reversed. Neither sulpiride nor SCH-23390 had any influence on the effect of HFS on veratridine-induced DA outflow. No effect of HFS on glutamate outflow was observed in all experiments. These results led us to suggest that in our model HFS primarily affects GABAergic neurons. These neurons are embedded in a neuronal network with a GABA-dopamine circuit, and thus, HFS interacts with a neuronal network, not only with one neurotransmitter system or one neuron population.     

Physiological presynaptic facilitation of dopamine release in the cat caudate nucleus

Using halothane-anaesthetized cats implanted with push-pull cannulae, we investigated the effects of GABA application into the VM/VL on the release of [3H] DA continuously synthetized from [3H] tyrosine in the ipsilateral CN and SN and on single unit activity of nigral DA cells. GABA was applied (30 min) at a concentration of 10(-3) or 10(-5) M since the higher concentration reduces the local multi-unit activity in the VM/VL while the opposite response is observed with the lower one. The application of GABA into the VM/VL at a concentration of 10(-3) M resulted in an increase in nigral [3H] DA release, an inhibition of DA cell firing and a decrease in [3H] DA release in the CN. The latter effect is likely due to the inhibition of DA neuron activity which is triggered through DA autoreceptors by DA released from dendrites. In contrast, when applied at a concentration of 10(-5) M into the VM/VL, GABA stimulated [3H] DA release in the CN despite its inhibitory effect on single unit activity of DA cells. Furthermore, the nigral release of [3H] DA was no longer affected. These results indicated that DA release from nerve terminals was not dependent on nerve activity and they favour the existence of a potent facilitatory presynaptic regulation of DA release. The intervention of a presynaptic mechanism was further established by examining the effect of GABA (10(-5) M) application into the VM/VL on [3H] DA release in the CN shortly after a complete ipsilateral hemisection of the brain made at the meso-diencephalic level.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ethylenediamine and GABA Potentiation of [3H]Diazepam Binding to Benzodiazepine Receptors in Rat Cerebral Cortex

Specific binding of [3H]diazepam at a free concentration of 2 nM was found to be maximally potentiated by 117% in Tris-HCl buffer and 160% in Tris-citrate buffer by ethylenediamine (EDA), but only at relatively high concentrations of EDA (ED50 = 5 X 10(-5) M), although this potentiation was susceptible to a low dose (6 microM) of bicuculline. Dose-response curves show that EDA differs from GABA with respect to both potency and efficacy. In additivity experiments no evidence was found that EDA could act as a partial agonist at GABA receptors, and it was concluded that EDA and GABA apparently do not potentiate [3H]diazepam binding by acting on the same receptor. Scatchard analysis lends support to this hypothesis, indicating that the potentiation of [3H]diazepam binding by 3.16 X 10(-3) M EDA is due to an increase in receptor number (from 930 to 1170 fmol/mg protein) and not receptor affinity (remaining constant about 20 nM). Subsequent studies showed the potentiation to be reversible. It is concluded that EDA can act on the GABA-benzodiazepine receptor ionophore complex but that this is probably not a direct action on the GABA receptor. It is suggested that EDA can be used to differentiate GABA receptors linked to benzodiazepine receptors from those not so linked.     

The bicuculline-like properties of dopamine sulfate in rat brain

To determine whether the convulsive action of intraventricularly injected dopamine sulfate, a dopamine metabolite present in rat brain and human cerebrospinal fluid, could be due to its interaction with GABAergic pathway, we compared the convulsive effect of dopamine sulfate with that of bicuculline in the conscious rat and determined the interaction of dopamine sulfate with [3H] GABA binding and uptake in rat brain tissues. The results showed that the convulsive effects of dopamine sulfate and of bicuculline could be abolished by GABA agonists diazepam and muscimol, but not by DA antagonists haloperidol and metoclopramide. In addition they were additive. Both dopamine 3-O-sulfate and dopamine-4-O-sulfate, like bicuculline, could displace sodium-independent [3H] GABA binding to rat brain synaptic membranes (IC50 = 400 microM) but had no action on GABA uptake. DA sulfate had no effect on [3H] strychnine binding to rat brain homogenates. This evidence together with the structural resemblance between dopamine sulfate and GABA suggested that the convulsive activity of dopamine sulfate may result from its interaction with central GABA receptors.     

Chronic neuroleptic treatment in rats produces persisting changes in GABAA and dopamine D-2, but not dopamine D-1 receptors

The effects of continuous treatment with haloperidol (HAL) or fluphenazine (FLU) for 10 months on dopamine and GABA receptors in the rat brain was examined using in vitro autoradiography. Rats treated with HAL, but not FLU, showed an increase in D-2 receptor binding in the caudate-putamen as revealed by [3H]spiperone. Labeling of D-1 receptors by [3H]SCH23390 revealed no changes in either drug-treated group. Both drug-treated groups, however, exhibited a significant increase in [3H]muscimol binding in substantia nigra, pars reticulata (SNR). These dopaminergic-GABAergic receptor alterations may be related to previously reported changes in oral movement activity seen in these neuroleptic-treated animals.     

Chronic treatment with high doses of haloperidol fails to decrease the time course for the development of depolarization inactivation of midbrain dopamine neurons

Using extracellular single unit recording techniques, we investigated the effects produced by chronic treatment with high doses of haloperidol (CHAL, 5 mg/kg/day, s.c.) on midbrain dopamine (DA) neuronal activity. This regimen of HAL treatment produced a time-dependent reduction in the number of spontaneously active DA neurons. Additionally, this dose regimen induced an irregular firing pattern in many of the remaining active DA neurons in both the ventral tegmental area (A10) and substantia nigra pars compacta (A9) regions. These effects were comparable to those obtained previously in rats treated chronically with lower doses of HAL (0.5 mg/kg/day, s.c.). However, there was a greater decrease in the number of spontaneously active DA cells detected in rats treated with high doses of HAL for three weeks compared to those receiving the low doses. On the other hand, higher doses of apomorphine (200 micrograms/kg, i.v.) were required to reverse both the reduction of DA activity and irregular discharge pattern in rats treated chronically with high doses of HAL. In conclusion, the results of the present study substantiate the view that CHAL-induced depolarization inactivation (DI) of DA neurons is a time-dependent process and chronic treatment with high doses of HAL did not shorten the time course required for the development of DI on the majority of midbrain DA neurons.