急性低血压对清醒大鼠前庭内侧核区γ-氨基丁酸和甘氨酸含量的影响

为了探讨急性低血压通过外周前庭器官影响前庭神经核活动的部分神经化学机制,本实验利用脑部微量透析法和高效液相色谱法,观察静脉注射硝普钠(sodium nitroprusside,SNP)诱发急性低血压时,清醒大鼠前庭内侧核(medial vesti-bular nucleus,MVN)内γ-氨基丁酸(γ-aminobutyric acid,GABA)和甘氨酸(glycine,Gly)含量的变化。实验选用Wistar雄性清洁级大鼠72只,体重在(250±50)g,随机分为对照组、前庭器官损伤同侧组和前庭器官损伤对侧组。实验观察到,静脉注射SNP使血压平均下降30%时,MVN内GABA和Gly含量明显减少(P0.01)。用对氨基苯胂酸盐破坏单侧外周前庭器官两周后,静脉注射SNP使血压降低30%后,单侧前庭器官破坏同侧MVN内GABA和Gly含量无明显变化;而单侧前庭器官破坏对侧MVN内GABA和Gly含量明显减少(P0.01)。上述结果提示,清醒动物诱发急性低血压影响MVN功能活动过程中可能有GABA和Gly的参与。     

单侧迷路破坏后大鼠前庭神经内侧核区氨基酸含量的变化

本实验用脑部微量透析法和高效液相色谱法观察单侧迷路破坏(unilateral labyrinthectomy,经利多卡因或对氨基苯胂酸盐预处理以阻断单侧外周前庭器官)后大鼠同侧及对侧前庭神经内侧核(medial vestibular nucleus,MVN)区部分氨基酸(天冬氨酸、谷氨酸、谷氨酰胺、甘氨酸、牛磺酸和丙氨酸)含量的变化,以了解前庭代偿的部分神经化学机制.实验观察到,对照组大鼠MVN区天冬氨酸、谷氨酸、谷氨酰胺、甘氨酸、牛磺酸和丙氨酸浓度分别为(6.15±0.59),(18.13±1.21),(33.73±1.67),(9.26±0.65),(9.56±0.77)和(10.07±0.83)pmol/8 μL透析样本.左侧中耳内灌注2%利多卡因后10 min,同侧MVN区天冬氨酸、谷氨酸含量立即减少(P＜0.05),牛磺酸含量增加(P＜0.05);对侧MVN区谷氨酸含量立即增加(P＜0.05),甘氨酸和丙氨酸含量减少;双侧核团间谷氨酸、甘氨酸和丙氨酸含量失衡.而用对氨基苯胂酸盐永久阻断单侧前庭器官2周后,同侧MVN区谷氨酸和丙氨酸含量减少,谷氨酰胺含量增高;对侧MVN区谷氨酸含量也减少;同侧MVN区谷氨酰胺含量明显高于对侧MVN区.结果提示,单侧迷路破坏后双侧MVN区氨基酸含量立即失去平衡,随着前庭代偿的进展,此差异减少,但是在前庭代偿后却出现双侧前庭核区谷氨酰氨的含量失衡,说明在前庭代偿过程中氨基酸含量变化起着重要作用.     

荧光高效液相色谱法测定三种失眠模型大鼠脑组织氨基酸类神经递质的含量

目的测定睡眠剥夺大鼠脑组织氨基酸类神经递质的含量。方法复制药物诱导失眠动物模型、平台水环境诱导失眠动物模型、刺激诱导失眠动物模型,以Agilent 1100荧光检测器高效液相系统为检测工具,Agilent ZORBAX SB-Aq(250 mm×4.6 mm,5μm)为色谱柱,柱温25℃,激发波长λex=357 nm,发射波长λem=455 nm,甲醇-50 mmoL/L醋酸钠缓冲液(pH=6.5)为流动相,采取梯度洗脱,测定正常组及模型组大鼠脑组织中谷氨酸(Glu)、甘氨酸(Gly)、γ-氨基丁酸(γ-GABA)、牛磺酸(Tau)的含量。结果谷氨酸、甘氨酸、γ-氨基丁酸、牛磺酸分别在10.06～0.0503、10.13～0.0506、10.05～0.0502、10.03～0.0501μg/mL范围内,其浓度与峰面积呈良好的线性关系(r分别为0.99995、0.99995、0.99985、0.99990)。测得药物诱导失眠大鼠脑组织中Glu、Gly、Tau、γ-GABA的含量为(0.2042±0.0145)、(0.0086±0.0005)、(0.0919±0.0024)、(0.0421±0.0011)μg;平台水环境诱导失眠大鼠脑组织中Glu、Gly、Tau、γ-GABA的含量为(0.2144±0.0159)、(0.0085±0.0004)、(0.0966±0.0035)、(0.0433±0.0012)μg;刺激诱导失眠大鼠脑组织中Glu、Gly、Tau、γ-GABA的含量为(0.1818±0.0043)、(0.0084±0.0005)、(0.0824±0.0033)、(0.0414±0.0018)μg;正常大鼠脑组织中Glu、Gly、Tau、γ-GABA的含量为(0.1744±0.0038)、(0.0085±0.0004)、(0.0791±0.0022)、(0.0406±0.0012)μg。结论本实验建立的方法能满足同时测定大鼠脑组织中谷氨酸、甘氨酸、γ-氨基丁酸、牛磺酸的含量测定的需要,Glu、Tau、γ-GABA与失眠可能存在一定的量效关系,三种失眠动物模型均能较好的反映出脑内氨基酸类神经递质的变化。     

高效液相荧光法测定大鼠脑内氨基酸类神经递质方法的改良

目的 改良测定大鼠脑组织氨基酸类神经递质的反相高效液相色谱荧光法.方法 改良使用磷酸盐-甲醇-乙腈作为流动相,反相高效液相色谱洗脱,高丝氨酸作为内标,邻苯二甲醛柱前衍生和荧光检测器,检测大鼠大脑皮质、海马、纹状体、中脑、小脑和下丘脑6个脑区中天冬氨酸(Asp)、谷氨酸(Glu)、谷氨酰胺(G1n)、甘氨酸(Gly)、γ-氨基丁酸(GABA)和牛磺酸(Tau)6种氨基酸类神经递质含量.结果 6种氨基酸在20 min内洗脱完全,分离效果良好;在6.25～ 400 μmol/L浓度范围有较好的线性关系,其相关系数不低于0.99;6种氨基酸日内试验精密度范围为1.38％ ～7.59％;日间试验精密度为2.7％～8.68％;6种氨基酸回收率不低于80％.结论 改良后的反相高效液相色谱荧光法灵敏度较高、重复性好,能有效分离检测大鼠脑组织分区中氨基酸类神经递质含量.     

谷氨酸是哺乳动物中枢的一种神经递质

哺乳动物中枢存在高亲和摄取谷氨酸(Glu)和门冬氨酸(Asp)系统。Glu 突触前定位于特异的神经元,生理性刺激能使 Glu 从突触前膜释出,作用于酸性氨基酸的受体,引起突触后的反应,而且具有迅速终止递质作用的机制。外源性给予 Glu 及其摹拟剂,能产生与内源性 Glu 相同的效应,同样可被受体拮抗剂阻断。Glu 具备神经递质必需的条件,是哺乳动物中枢的兴奋性递质。     

新生、成年和老年小鼠大脑皮层突触小体神经递质氨基酸含量的比较研究

用DANS反应-薄膜层析-萤光方法测定了蔗糖密度梯度超离心制备的不同年龄小鼠大脑皮层突触小体中递质氨基酸的含量。实验结果表明:(1)不同年龄小鼠每克皮层组织中突触小体蛋白质含量不同。新生——5.68、成年——21.37、老年——19.14毫克/克脑组织湿重。(2)递质氨基酸含量以毫微克分子/克脑组织湿重表示时,GABA 含量在发育期升高,到老年期又降低;牛磺酸含量由新生到老年期持续下降;谷氨酸、天冬氨酸含量在发育期升高,到老年期无明显变化。(3)突触小体中“抑制性”递质氨基酸总量与“兴奋性”递质氨基酸总量的比值(GABA Tau Gly/Glu Asp)随年龄增长而明显降低,成年的比值趋近于1。新生——3.39、成年——1.06、老年——0.79。(4)老年小鼠皮层突触小体的蔗糖梯度区带明显分成两层。即除P_2B 层外,出现明显的P_2B' 层,其GABA、谷氨酸、天冬氨酸含量与P_B 层相比,分别降低24.2%(P<0.05)、50.4%(P<0.001)和44%(P<0.001)。     

新生、成年和老年小鼠大脑皮层突触小体神经递质氨基酸含量的比较研究

用DANS反应-薄膜层析-萤光方法测定了蔗糖密度梯度超离心制备的不同年龄小鼠大脑皮层突触小体中递质氨基酸的含量。实验结果表明:(1)不同年龄小鼠每克皮层组织中突触小体蛋白质含量不同。新生——5.68、成年——21.37、老年——19.14毫克/克脑组织湿重。(2)递质氨基酸含量以毫微克分子/克脑组织湿重表示时,GABA含量在发育期升高,到老年期又降低;牛磺酸含量由新生到老年期持续下降;谷氨酸、天冬氨酸含量在发育期升高,到老年期无明显变化。(3)突触小体中“抑制性”递质氨基酸总量与“兴奋性”递质氨基酸总量的比值(GABA Tau Gly/Glu Asp)随年龄增长而明显降低,成年的比值趋近于1。新——3.39、成年——1.06、老年——0.79。(4)老年小鼠皮层突触小体的蔗糖梯度区带明显分成两层。即除P_2B层外,出现明显的P_2B′层,其GABA、谷氨酸、天冬氨酸含量与P_2B层相比,分别降低24.2%(P<0.05)、50.4%(P<0.001)和44%(P<0.001)。     

DGMI对缺血再灌注大鼠脑内神经递质的影响

为了探讨银杏二萜内酯葡胺注射液(DGMI)对缺血再灌注大鼠脑内神经递质的影响。本研究将SPF级SD雄性大鼠60只,随机分为6组,造模与给药结束后,使用高效液相-电化学的方法检测实验大鼠的氨基酸类与单胺类神经递质含量。大鼠脑组织的ImageJ图像分析发现,高剂量组大鼠的梗死体积与水肿面积显著低于模型组,并与空白组水平接近。高剂量组大鼠的Asp、Glu、GABA水平最接近空白组,认为高剂量组调节氨基酸类神经递质平衡的效果最佳。高剂量组大鼠的DA、E、NE与空白组比较无差异,认为高剂量组的治疗效果显著优于阳性对照药物。本研究表明,银杏二萜内酯葡胺注射液可以有效抑制兴奋性神经递质与单胺类神经递质的释放,增加脑内抑制性神经递质的含量,推测DGMI可以通过调节氨基酸类神经递质的平衡,从而对脑组织神经元进行保护。     

猫初级视皮层内Glu／GABA表达比率的衰老性变化

最近的一些研究结果显示,视皮层内抑制性递质系统作用减弱可能是导致老年性视觉功能衰退的重要因素。是否皮层内兴含性递质系统办伴随衰老而发生改变并影响皮层内神经兴奋与抑制的平衡尚不清楚。为此,利用Nissl染色和免疫组织化学染色方法以及Image—Pro Express图像分析软件对青、老年猫初级视皮层（17区）内各层神经元密度、兴奋性递质谷氦酸免疫反应阳性（Glu—immunoreactive,Glu—IR）神经元密度以及抑制性递质γ-氨基丁酸免疫反应阳性（v．aminobutyric acid-immunoreactive,GABA—IR）神绎元密度进行了统计分析。结果显示,青、老年猫初级视皮层各层神经元密度均没有明显的年龄性差异（P〉0．05）;与青年猫相比,老年猫初级视皮层Glu—IR、GABA．IR神经元密度均显著减少（P〈0．01）,而Glu—IR／GABA-IR神经元密度比率却显著增大（P〈0．01）。结果提示,老年猫初级视皮层内兴奋性递质系统作用相对增强,而抑制性递质系统的作用相对减弱,导致皮层内兴奋-抑制平衡关系失调,这可能是引起老年个体视觉功能衰退的重要原因之一。     

2,6-二异丙基苯酚逆转嗅球切除抑郁模型大鼠电休克后的Tau蛋白过度磷酸化和认知障碍

通过观察2, 6-二异丙基苯酚对电休克后嗅球切除抑郁模型大鼠学习记忆和Tau蛋白过度磷酸化的影响,探讨兴奋性氨基酸受体拮抗剂对Tau蛋白过度磷酸化的调节及两者对抑郁大鼠学习记忆的影响,为改善学习记忆障碍的神经心理学机制研究和临床干预性治疗提供实验依据．按随机单位组2×2析因设计设置2个干预因素,即电休克干预(两水平：无处置、施行一个疗程电休克)和2, 6-二异丙基苯酚干预(两水平：腹腔注射5 ml 生理盐水或5 ml 2, 6-二异丙基苯酚100 mg/kg)的所有组合．选24周龄健康雄性Sprague-Dawley大鼠建立嗅球切除抑郁模型,将32只24周龄模型大鼠随机分为4个实验组(n=8):Ⅰ组(腹腔注射5 ml 2, 6-二异丙基苯酚100 mg/kg)、Ⅱ组(腹腔注射5 ml 2, 6-二异丙基苯酚100 mg/kg +施行电休克1个疗程)、Ⅲ组(腹腔注射5 ml 生理盐水)、Ⅳ组(腹腔注射5 ml 生理盐水+施行电休克1个疗程)．全部电休克处置结束24 h内开始Morris水迷宫检测,之后留取海马组织．高效液相色谱法检测神经递质谷氨酸(Glu)在海马组织中的含量;免疫组化SP法和蛋白质印迹法检测Tau-5(总Tau蛋白)、p-PHF1^Ser396/404、p-AT8^Ser199/202、p-12E8^Ser262、GSK-3β^1H8和PP-2A在海马组织神经元中的表达．电休克和2, 6-二异丙基苯酚均可造成大鼠学习记忆障碍,即延长逃避潜伏期并缩短空间探索时间,两者的影响呈相减效果．电休克可明显增加海马中神经递质谷氨酸(Glu)的浓度,2, 6-二异丙基苯酚可降低海马中神经递质Glu的浓度,且两者有相减效果．电休克和2, 6-二异丙基苯酚对海马总Tau蛋白和PP-2A蛋白的表达无明显影响．电休克可增加海马中磷酸化Tau蛋白和GSK-3β^1H8蛋白的表达;2, 6-二异丙基苯酚可减少海马中磷酸化Tau蛋白和GSK-3β^1H8蛋白的表达;两者的影响均呈相减效果．实验结果表明,电休克导致海马Glu浓度升高,通过上调GSK-3β^1H8增加海马Tau蛋白的磷酸化程度导致学习记忆功能障碍,而2, 6-二异丙基苯酚则可通过降低海马Glu浓度下调GSK-3β1H8的表达,从而减缓Tau蛋白的磷酸化程度以改善ECT后的学习记忆．     

In vivo release patterns and cardiovascular properties of inhibitory and excitatory amino acids in the hypothalamus

Summary The posterior hypothalamus of conscious, freely moving rats was superfused with artificial cerebrospinal fluid through a push-pull cannula and the release of amino acids was determined in the superfusate. Under basal conditions, the release rates of taurine, GABA and glutamate fluctuated according to ultradian rhythms with different frequencies. Hypothalamic superfusion with veratridine or high concentrations of potassium choride enhanced the release rates of taurine, GABA and glutamate in a concentration-dependent way. Tetrodotoxin decreased the basal release rates of the three amino acids. The release of arginine was not influenced significantly by these compounds. A fall of blood pressure elicited by intravenous infusion of nitroprusside decreased the release rates of GABA and taurine and enhanced the release of glutamate. Infusion of noradrenaline increased blood pressure and release rates of GABA and taurine, while the release of glutamate was not influenced. Neither the pressor, nor the depressor responses to drugs influenced the release of arginine in the hypothalamus. It is concluded that the inhibitory amino acids taurine and GABA released from hypothalamic neurons possess a tonic hypotensive function. The excitatory amino acid glutamate, released from glutamatergic neurons of the hypothalamus, seems to possess a hypertensive function in counteracting a fall of blood pressure.This work was supported by the Fonds zur Förderung der wissenschaftlichen Forschung. These results were presented at the Third International Congress on Amino Acids, Vienna, August 1993     

Dopaminergic Modulation of Glutamate Release in Striatum as Measured by Microdialysis

Glutamate and aspartate are the primary neurotransmitters of projections from motor and premotor cortices to the striatum. Release of glutamate may be modulated by dopamine receptors located on corticostriatal terminals. The present study used microdialysis to investigate the dopaminergic modulation of in vivo striatal glutamate and aspartate release in the striatum of awake-behaving rats. Local perfusion with a depolarizing concentration of K+ through a dialysis probe into the rat striatum produced a significant increase in the release of glutamate, aspartate, and taurine. The D2 agonist LY171555 blocked the K(+)-induced release of glutamate and aspartate, but not taurine, in a concentration-dependent manner. The D1 agonist SKF 38393 did not alter K(+)-induced release of glutamate and taurine, but did significantly decrease aspartate release. Neither agonist had any effect on basal amino acid release. The D2 antagonist (-)-sulpiride reversed the inhibitory effects of LY 171555 on K(+)-induced glutamate release. These results provide in vivo evidence for a functional interaction between dopamine, the D2 receptor, and striatal glutamate release.     

Reduction of brain taurine: Effects on neurotoxic and metabolic actions of kainate

The effects of chronic administration of 2-guanidinoethane sulfonic acid on the levels of intra- and extracellular amino acids in the rat hippocampus were studied. The tissue content of taurine was selectively reduced by almost one third after 9 days of peroral administration of 1% 2-guanidinoethane sulfonate. Extracellular levels of amino acids were monitored with the brain microdialysis method. The taurine concentration in the extracellular fluid was depressed in relation to the decrease in intracellular taurine. Unexpectedly, extracellular (but not intracellular) glutamate was doubled in 2-guanidinoethane sulfonate treated animals. The kainic acid evoked release of taurine was suppressed in the 2-guanidinoethane sulfonate group, whereas the kainate stimulated efflux of glutamate was elevated after 2-guanidinoethane sulfonate administration. The acute metabolic effects of kainate were studied by measuring the efflux of the adenosine triphosphate breakdown products hypoxanthine, xanthine, inosine and adenosine. No differences were found between control and 2-guanidinoethane sulfonate treated rats with respect to basal or kainic acid evoked release of purine catabolites. Also, the neuronal loss caused by kainate injection into the hippocampus was not modified by 2-guanidinoethane sulfonate treatment, suggesting that endogenous taurine does not affect these responses. We conclude that chronic administration of 2-guanidinoethane sulfonate does not sensitize central neurons to the metabolic and toxic actions of kainate.     

In vivo co-ordinated interactions between inhibitory systems to control glutamate-mediated hippocampal excitability

We present an overview of the long-term adaptation of hippocampal neurotransmission to cholinergic and GABAergic deafferentation caused by excitotoxic lesion of the medial septum. Two months after septal microinjection of 2.7 nmol alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA), a 220% increase of GABA(A) receptor labelling in the hippocampal CA3 and the hilus was shown, and also changes in hippocampal neurotransmission characterised by in vivo microdialysis and HPLC. Basal amino acid and purine extracellular levels were studied in control and lesioned rats. In vivo effects of 100 mm KCl perfusion and adenosine A(1) receptor blockade with 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) on their release were also investigated. In lesioned animals GABA, glutamate and glutamine basal levels were decreased and taurine, adenosine and uric acid levels increased. A similar response to KCl infusion occurred in both groups except for GABA and glutamate, which release decreased in lesioned rats. Only in lesioned rats, DPCPX increased GABA basal level and KCl-induced glutamate release, and decreased glutamate turnover. Our results evidence that an excitotoxic septal lesion leads to increased hippocampal GABA(A) receptors and decreased glutamate neurotransmission. In this situation, a co-ordinated response of hippocampal retaliatory systems takes place to control neuron excitability.     

The use of microdialysis for studying the regional effects of pharmacological manipulation on extracellular levels of amino acids--some methodological aspects.

The purpose of this study was to examine and validate the use of microdialysis for sampling and pharmacologically manipulating extracellular amino acids in the brain. Repeated use of microdialysis probes in acute intracerebral experiments did not significantly alter the relative recovery in vitro for the amino acids quantitated (GABA, aspartate, glutamate, glycine, taurine, and alanine). Regional differences in basal levels of some of the amino acids were detected in dialysates collected from the dorsomedial hypothalamus, striatum, and frontal cortex. The percent in vitro recoveries for the amino acids from the probes used in the three regions were not significantly different suggesting that the regional differences in basal levels of amino acids were functionally derived and not a consequence of variations in probe recovery. Perfusion with nipecotic acid, an inhibitor of GABA uptake, resulted in selective elevations in extracellular GABA in the three regions studied. Conversely, perfusion with high-potassium, a depolarizing agent, resulted in significant elevations in not only extracellular GABA but also aspartate, glutamate, and taurine. Thus, microdialysis is a method which can be employed to assess and to pharmacologically manipulate extracellular amino acids in the rat brain.     

Amino acids modulate the hypotensive effect of angiotensin-(1-7) at the caudal ventrolateral medulla in rats

The present experiment was designed to investigate the possible involvement of glutamate and taurine in the depressor response produced by angiotensin (Ang)-(1-7) at the caudal ventrolateral medulla (CVLM) in rats anesthetized with urethane and alpha-chloralose. Microinjection of Ang-(1-7) into the CVLM elicited a depressor response which was partially blocked by nonselective glutamate receptors antagonist kynurenic acid, whereas selective Ang-(1-7) antagonist Ang779 produced a pressor response which was significantly attenuated by taurine receptors antagonist 6-aminomethyl-3-methyl-4H-1,2,4-benzothiadiazine-1,1-dioxide. Release of glutamate and taurine in the CVLM was evaluated with microdialysis, and the contents of these amino acids were measured with high performance liquid chromatography-fluorescent detection. The depressor response to Ang-(1-7) was accompanied by an increased release of glutamate and a decrease of taurine at the CVLM, whereas the pressor response to Ang779 was associated with a decreased release of glutamate and an increase of taurine. These results suggest that Ang-(1-7) and its antagonist Ang779 modulate the release of glutamate and taurine at the CVLM, which in turn contributes at least in part to the blood pressure response to Ang-(1-7) and Ang779.     

Rapid Communication: Adrenalectomy Attenuates Stress-Induced Elevations in Extracellular Glutamate Concentrations in the Hippocampus

Abstract— Glucocorticoids and stress have deleterious effects on hippocampal cell morphology and survival. It has been hypothesized that these effects are mediated via an excitatory amino acid mechanism. The present study was designed to evaluate the effects of acute stress on the extracellular levels of glutamate in the hippocampus and to determine if adrenalectomy modifies this response. Rats were adrenalectomized or sham-adrenalectomized and implanted with microdialysis probes in the CAS region of the hippocampus. Three days later rats were subjected to an acute 1 -h period of immobilization stress. Stress significantly increased extracellular glutamate levels in the sham-operated rats, which peaked at 20 min following the initiation of stress. Extracellular glutamate levels also increased immediately following the termination of stress. In the adrenalectomized rats there was a 30% decrease in basal extracellular concentrations of glutamate and a marked attenuation (-70%) of the stress-induced increase in extracellular glutamate levels. Extracellular concentrations of taurine were not modified by adrenalectomy and did not change in response to stress. These results suggest that glucocorticoid-in-duced elevations in extracellular glutamate concentrations may contribute to the deleterious effects of stress on hippocampal neurons.     

Chronic administration of valproic acid induces a decrease in rat striatal glutamate and taurine levels

Summary The effect of acute and chronic (10 days) administration of 200 mg/kg (i.p.) of valproic acid (VPA) on endogenous levels of aspartate, glutamate, alanine, glycine and taurine in the cerebral frontal cortex and corpus striatum of rats was studied. Quantification of the amino acid levels was performed by HPLC.Valproic acid (VPA) did not either induce changes on these neurotransmitters contents in corpus striatum after acute treatment. After chronic administration we found a decrease on the endogenous levels of glutamic acid (24%, p < 0.05) which was related to an increase (250%, p < 0.02) of the in vitro KCl evoked release of glutamate. We found decrements in taurine endogenous levels (22%, p < 0.05) which was not associated with an increase of its release.In cerebral frontal cortex there was not found any change neither under the acute nor under the chronic condition.Thus, it may be conclude that chronic treatment with VPA produces decreases on the endogenous levels of glutamate and taurine. However the relevance of this effect concerning it therapeutic action remains unclear.     

Mechanisms of enhanced taurine release under Ca2+ depletion

The sulfur-containing amino acid taurine is an inhibitory neuromodulator in the brain of mammals, as well as a key substance in the regulation of cell volumes. The effect of Ca(2+) on extracellular taurine concentrations is of special interest in the context of the regulatory mechanisms of taurine release. The aim of this study was to characterize the basal release of taurine in Ca(2+)-free medium using in vivo microdialysis of the striatum of anesthetized rats. Perfusion of Ca(2+)-free medium via a microdialysis probe evoked a sustained release of taurine (up to 180 % compared to the basal levels). The Ca(2+) chelator EGTA (1mM) potentiated Ca(2+) depletion-evoked taurine release. The substitution of CaCl(2) by choline chloride did not alter the observed effect. Ca(2+)-free solution did not significantly evoke release of taurine from tissue loaded with the competitive inhibitor of taurine transporter guanidinoethanesulfonate (1mM), suggesting that in Ca(2+) depletion taurine is released by the transporter operating in the outward direction. The volume-sensitive chloride channel blocker diisothiocyanostilbene-2,2'-disulfonate (1mM) did not attenuate the taurine release evoked by Ca(2+) depletion. The non-specific blocker of voltage-sensitive Ca(2+) channels NiCl(2) (0.65 mM) enhanced taurine release in the presence of Ca(2+). CdCl(2) (0.25 mM) had no effect under these conditions. However, both CdCl(2) and NiCl(2) attenuated the effect of Ca(2+)-free medium on the release of taurine. The data obtained imply the involvement of both decreased influx of Ca(2+) and increased non-specific influx of Na(+) through voltage-sensitive calcium channels in the regulation of transporter-mediated taurine release in Ca(2+) depletion.