Taurine and GABA release from mouse cerebral cortex slices: Effects of structural analogues and drugs

The effects of structural analogues, excitatory amino acids and certain drugs on spontaneous and potassium-stimulated exogenous taurine and GABA release were investigated in mouse cerebral cortex slices using a superfusion system. Spontaneous efflux of both amino acids was rather slow but could be enhanced by their uptake inhibitors. Taurine efflux was facilitated by exogenous taurine, hypotaurine, -alanine and GABA, whereas GABA, nipecotic acid and homotaurine effectively enhanced GABA release. The stimulatory potency of the analogues closely corresponded to their ability to inhibit taurine and GABA uptake, respectively, indicating that these efflux processes could be mediated by the carriers operating outwards. Glutamate induced GABA release, whereas taurine efflux was potentiated by aspartate, glutamate, cysteate, homocysteate and kainate. The centrally acting drugs, including GABA agonists and antagonists, as well as the proposed taurine antagonist TAG (6-aminomethyl-3-methyl-4H-1,2,4-benzothiadiazine-1,1-dioxide), had no marked effects on spontaneous taurine and GABA release. Potassium ions stimulated dosedependently both taurine and GABA release from the slices, the responses of taurine being strikingly slow but sustained. Exogenous GABA and nipecotic acid accelerated the potassium-stimulated GABA release, whereas picrotoxin and bicuculline were ineffective. The potassium-stimulated taurine release was unaltered or suppressed by exogenous taurine and analogues, differing in this respect from GABA release. The apparent magnitude of the depolarization-induced GABA release is thus influenced by the function of membrane transport sites, but the same conclusion cannot be drawn with regard to taurine. Haloperidol and imipramine were able to affect the evoked release of both taurine and GABA.     

Fluorometrical Analysis of Guanidino Compounds in Human Cerebrospinal Fluid

Abstract: Guanidino compounds in CSF of 57 human subjects were determined fluorometrically after reaction with phenanthrenequinone in alkali solution, using HPLC. Creatinine (65.2 ± 13.4 nmol/ml), arginine (24.7 ± 6.4 nmol/ml), and homoarginine (0.7 ± 0.3 nmol/ml) were found in all subjects. Trace amounts of guanidinosuccinic acid and guanidinoacetic acid were detected in some of the subjects. Brain guanidino compounds, taurocyamine, N -acetylarginine, and methylguanidine were not detected in CSF.     

Taurine and its Trophic Effects in the Retina Lucimey Lima

The sulphur amino acid taurine possesses variable functions during development and regeneration of the central nervous system. The retina synthesize and uptake taurine, which is the amino acid present in the highest concentration in this tissue. Deficiency of taurine alters the structure and the function of the cerebral and cerebelar cortex, as well as the retina. Taurine increases outgrowth of postcrush goldfish retina in culture, partially by elevating calcium influx, and also by the modulation of protein phosphorylation. Its concentration increases in the retina after the lesion of the optic nerve, and the intraocular injection of it, between the crush and the explantation, stimulates the outgrowth of neurites. Taken together, although there are a great number of unresolved questions on the mechanisms of action of this amino acid as atrophic substance, the results support the role of taurine during regeneration of the optic nerve.     

Calcium Modulates Osmosensitive Taurine Efflux in HeLa Cells

The role of Ca²⁺ in the signaling transduction pathway involved in osmosensitive taurine efflux in HeLa cells was studied using radiotracer efflux techniques. Taurine efflux induced by extracellular hypotonicity was decreased by 85% by removal of extracellular Ca²⁺ and simultaneous depletion of intracellular Ca²⁺ stores with thapsigargin. Extracellular Ca²⁺ removal, thapsigargin treatment, or addition of Gd³⁺ all decreased taurine efflux by ～50%. To explore the putative signal transduction pathways involved in swelling-induced taurine efflux, HeLa cells were exposed to PP1, an inhibitor of the Src family of tyrosine kinases, the phospholipase C inhibitor U73122, the IP₃ receptor antagonist 2-APB, and the generic protein kinase C inhibitor chelerythrine. All of these treatments caused ～50% inhibition of taurine release in Ca²⁺-rich extracellular medium and ～85%–90% in Ca²⁺-free conditions. The inhibitors of the conventional protein kinase C isoforms BIM-1 and Gö6976 reduced taurine efflux to a lesser extent. Acute (10-min) exposure to the phorbol ester tetradecanoyl phorbol acetate (TPA) increased taurine efflux in 25%, whilst overnight exposure had an inhibitory effect decreasing efflux by 22%. A working model for activation of osmosensitive taurine efflux in HeLa cells involving different Ca²⁺ signaling pathways is presented.     

牛磺酸抗小鼠动脉粥样硬化的研究

为了探讨牛磺酸抗小鼠动脉粥样硬化的影响及可能机制,将C57BL/6J小鼠分成五组,正常对照组给予基础饲料喂养,高脂组给予高脂饲料,牛磺酸组分别给予含1.0%、3.0%和5.0%牛磺酸的高脂饲料,实验时间为90d。结果表明,高脂组小鼠主动脉内膜和肝脏发生了粥样硬化病变和脂肪变性,而牛磺酸组病变程度随剂量增大而减轻。高脂组较正常对照组血清及肝脏甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-c)、动脉硬化指数(AI)显著升高,高密度脂蛋白胆固醇(HDL-c)显著降低;牛磺酸组较高脂组显著改善。可见牛磺酸可通过改善脂质代谢紊乱发挥抗动脉粥样硬化的作用。     

Age-Related Retinal Degeneration in Animal Models of Aging: Possible Involvement of Taurine Deficiency and Oxidative Stress

There is strong evidence that the retina degenerates with age. Electroretinogram deficits and photoreceptor cell death and structural abnormalities have been observed in both animal and human studies of aging. The mechanism behind this phenomenon is a very interesting area for scientific and medical study. Current data support the link between retinal degeneration and increased oxidative stress. Taurine is a free amino acid found in high millimolar concentrations in the retina, and age-related deficiency in retinal levels of taurine may contribute to the retinal degeneration associated with age. Taurine acts as an antioxidant and taurine replenishment is known to alleviate oxidative stress in the retina. Thus taurine supplementation may be useful in the treatment of age-related retinal dysfunction.     

Effects of Pregnancy on the Contents of Water, Taurine, and Total Amino Nitrogen in Rat Cerebral Cortex

Plasma osmolality and the levels of water, taurine, and total amino nitrogen (detected as ninhydrin-positive substances) have been measured in the cerebral cortices of nonpregnant and 19-day pregnant Wistar rats. Plasma osmolality fell by 11 mosmol/kg during pregnancy. Brain water content remained unaltered, but levels of taurine and ninhydrin-positive substances fell by 48.5 and 21.9%, respectively. It is suggested that one way in which brain cells are prevented from swelling during the mild hypoosmolality of pregnancy is through loss of cellular amino nitrogen, particularly taurine.     

Effect of GABAmimetics on electrocorticographic spike discharges induced by guanidinoethanesulfonic acid (amidino-taurine) in the rat

The effect of guanidinoethanesulfonic acid (GES) on rat electrocorticograms (ECoG) and the effects of -aminobutyric acid (GABA) and GABA-agonists on the ECoG changes induced by GES were studied. Sporadic spike discharges began 2–5 min after 1 mol GES/10 l on filter paper was applied to the pia mater of the left sensorimotor cortex; spike discharges extended to the opposite cerebral hemisphere 60 min after the onset of the ipsilateral spike discharges. The spike discharges with a frequency of 5–10 spikes/min lasted until the end of the 4 hour recording. The induced spike discharges were suppressed when the original GES soaked filter paper was replaced by one containing GES (1 mol) supplement combined with taurine (1 mol/10 l). GABA (1 mol) and its receptor agonist, muscimol (10nmol) and (3R)-(–)-4-amino-3-hydroxybutyric acid (1 mol) also suppressed the GES-induced spike discharges when applied topically. Diazepam (DZP) (10 mg/kg) suppressed the GES-induced spike discharges 10 min after i.p. injection, but phenobarbital (20 mg/kg) increased the frequency and voltage of spike discharges 100 min following subcutaneous administration. Intraperitoneal injection of either valproate (200 mg/kg) or phenytoin (25 mg/kg), after the completion of the spike discharges, showed no effect. These findings suggest that neurotransmission or neuromodulatory effects of taurine participate in GES-induced seizure activity, and that GABA_A and DZP receptors may play a role in the mechanism that suppresses GES-induced seizures.     

Inhibition of ERK and JNK Decreases Both Osmosensitive Taurine Release and Cell Proliferation in Glioma Cells

Cell swelling is associated with the activation of an increase in the osmosensitive taurine release (OTR) rate, which serves to decrease cell volume as part of a process known as regulatory volume decrease. OTR, which is sensitive to many pharmacological agents including anion channel blockers and signalling pathway modulators, has also been suggested to play a role in cell cycle progression. At non-cytotoxic concentrations, the anion channel blocker NPPB (25 μM), the extra-cellular signal-regulated kinase inhibitor PD98059 (50 μM), and the c-Jun NH2-terminal kinase inhibitor SP 600125 (5 μM) each decreased the OTR rate by ≥50%, decreased cell proliferation, and increased G0/G1 cell cycle arrest.     

Taurine in the developing cat: Uptake and release in different brain areas

Taurine is an important modulator of neuronal activity in the immature brain. In kittens, taurine deficiency causes serious dysfunction in the cerebellar and cerebral visual cortex. The processes of taurine transport in vitro were now studied for the first time in different brain areas in developing and adult cats. The uptake of taurine consisted initially of two saturable components, high- and low-affinity, in synaptosomal preparations from the developing cerebral cortex and cerebellum, but the high-affinity uptake component completely disappeared during maturation. The release of both endogenous and preloaded labeled taurine from brain slices measured in a superfusion system was severalfold stimulated with a slow onset by depolarizing K⁺ (50 mM) concentrations. K⁺ stimulation released markedly more taurine from the cerebral cortex, cerebellum and brain stem in kittens than in adult cats. The responses were largest in the cerebellum. Both uptake and release of taurine are thus highly efficient in the brain of kittens and may be of significance in view of the vulnerability of cats to taurine deficiency.     

Ammonia-Induced Extracellular Accumulation of Taurine in the Rat Striatum In Vivo: Role of Ionotropic Glutamate Receptors

Accumulation of taurine (Tau), glutamate (Glu) and glutamine (Gln) was measured in vivo in microdialysates of the rat striatum following a direct application to the microdialysis tube of 60 mM ammonium chloride which renders the final ammonia concentration in the extracellular space to 5 mM. The following compounds were coadministered with ammonia to distinguish between the different mechanisms that may underlie the accumulation of amino acids: ion transport inhibitors, diisothiocyanostilbene-2,28-disulfonate (DIDS) and furosemide, a Glu transport inhibitor L-trans-pyrrolidine-2,4-dicarboxylate (PDC), an NMDA receptor antagonist dizocilpine (MK-801) and an 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/kainate (KA) receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX). Ammonia stimulated Tau accumulation in the microdialysates to 250% of the basal value. Furosemide did not significantly affect the stimulation by ammonia and DIDS only moderately depressed the effect. The ammonia-dependent Tau accumulation was increased by 50% in the presence of PDC and reduced by 35% in the presence dizocilpine and DNQX. In the microdialysates ammonia stimulated Glu and Gln accumulation somewhat less than Tau accumulation. Except for stimulation of Gln accumulation by DNQX, the effects were not modified by any of the cotreatments. The results are consistent with the assumption that ammonia stimulates Tau efflux mainly via activation of ionotropic Glu receptors.     

Free amino compounds and cell volume regulation in erythrocytes from different marine fish species under hypoosmotic conditions: the role of a taurine channel

Erythrocytes from the marine fish species ballan wrasse (Labrus berggylta Ascanius), bullhead (Myoxocephalus scorpius L.), cod (Gadus morhua L.), dab (Limanda limanda L.), eelpout (Zoarces viviparus L.), flounder (Platichthys flesus L.), lumpfish (Cyclopterus lumpus L.), plaice (Pleuronectes platessa L.), sole (Solea solea L.) and turbot (Scophthalmus maxima L.) possess the capacity for regulatory volume decrease. This property was demonstrated in vitro by reduction of the osmolality of the incubation medium from 330 to 255 mosmol·kg^-1. During the 4-h incubation period only the lumpfish cells completely regained the original volume. Twenty-seven free amino compounds were present in detectable amounts in the erythrocytes. At normal osmolality the taurine content was between 14.0 mol·g dry weight^-1 (lumpfish) and 147.4 mol·g dry weight^-1 (sole). Except in the bullhead, taurine was the quantitatively dominating amino compound in the erythrocytes from all species, and accounted for betwee 23% (lumpfish) and 88% (sole) of the total content of free amino compounds. In each species the regulatory volume decrease was associated with a reduction in the cellular content of taurine. Taurine contributed to between 6% (lumpfish) and 36% (flounder) of the cell shrinkage. There was a significant negative correlation, however, between the cellular concentration of taurine at normal osmolality and the capacity of the cells for regulatory volume decrease. Gamma-aminobutyric acid and/or glycine also contributed to the process of volume regulation, but to a lesser extent than taurine. The volume regulatory efflux of taurine and -aminobutyric acid were mediated by taurine channels. It is suggested that these channels also mediated the reduction in the cellular contents of glycine.Abbreviations cmp counts per minute - dw dry weight - GABA -amino-n-butyric acid - MW molecular weight - SD standard deviation - ww wet weight     

牛磺酸对小麦幼苗生长的生理效应

采用牛磺酸溶液培育小麦幼苗,测定10、100、500、1 000、5 000 mg/L的牛磺酸对小麦幼苗的光合作用PS Ⅱ光化学效率、细胞膜相对透性和膜脂过氧化以及生长的影响.结果表明,与对照组相比,适宜浓度的牛磺酸处理可促进小麦幼苗的生长,使其根长、株高、单株幼苗的干重和鲜重增加,并在一定程度上提高叶片的光化学效率,降低细胞膜相对透性和膜脂过氧化产物的含量;最适处理浓度约为500 mg/L.说明牛磺酸对小麦幼苗细胞膜有一定的保护作用.     

Effects of the barley mutants Risø 1508 and 527 high lysine genes on the cellular development of the endosperm

The dry grain weight of the Risø barley ( Hordeum vulgare L. var. disticum ) high lysine mutants 1508 and 527 at maturity was 32 and 37% lower, respectively, than the grains of the cultivar Bomi. Dry grain weight of the double mutant 527/1508 was reduced by 57%. Total number of endosperm nuclei from cv. Bomi, mutants 1508, 527 and 527/1508 at 24 days after anthesis was 173 000,156 000,121 000 and 111 000, respectively. Transverse mid-grain sections from mutants 1508 and 527 contained fewer aleurone cells and approximately the same number of starchy endosperm cells as cv. Bomi. The cellular organization of the endosperm of the double mutant deviated substantially from the normal. Cell volume in the central starchy endosperm of cv. Bomi, mutants 1508 and 527 at 33 days after anthesis averaged 390 000, 270 000 and 180 000 um5, respectively. Cell volume in the double mutant was smaller than in 527, but could not be accurately estimated due to the irregular shape of the cells. The mean section area of individual large starch granules in the central endosperm of mutants 1508, 527 and 527/1508 at 33 days after anthesis was 30, 48 and 72% smaller, respectively, than those of cv. Bomi. The average aleurone cell volume in cv. Bomi at 33 days after anthesis was 6 200 μm³.     

Taurine Release in the Developing and Adult Mouse Hippocampus: Involvement of Cyclic Guanosine Monophosphate

The inhibitory neuromodulator taurine is involved in osmoregulation and cell volume adjustments in the central nervous system. In addition, taurine protects neural cells from excitotoxicity and prevents harmful metabolic events evoked by cell-damaging conditions. The release of taurine in nervous cell preparations is greatly enhanced by glutamate receptor agonists and various cell-damaging conditions. NO-generating compounds also increase taurine release in the mouse hippocampus. The further involvement of the NO/cGMP pathway and protein kinases in preloaded [³H]taurine release from hippocampal slices from adult (3-month-old) and developing (7-day-old) mice in normoxia and in ischemia was now studied using a superfusion system. The release was enhanced by 8-Br-cGMP and the phosphodiesterase inhibitor 2-(2-propyloxyphenyl)-8-azapurin-6-one (zaprinast), particularly in the immature hippocampus, indicating that increased cGMP levels induce taurine release. The release was also increased by the inhibitor of soluble guanylyl cyclase, 1H-(1,2,4)oxadiazolo-(4,3a)quinoxalin-1-one (ODQ) and the protein kinase C activator 4-phorbol 12-myristate 13-acetate (PMA), but only in the adult hippocampus. The ischemia-induced release was also enhanced by increased cGMP levels in both adult and developing mice, whereas protein kinase inhibitors had no effects in any conditions. The results demonstrate that cGMP is able to modulate hippocampal taurine release in both adult and developing mice, the rise in cGMP levels evoking taurine release in normoxia and in ischemia. This could be part of the neuroprotective properties of taurine, being thus important particularly in cell-damaging conditions and in preventing excitotoxicity.     

Role of the Liver in Regulation of Body Cysteine and Taurine Levels: A Brief Review

The first-pass metabolism of dietary sulfur amino acids by the liver and the robust upregulation of hepatic cysteine dioxygenase activity in response to an increase in dietary protein or sulfur amino acid level gives the liver a primary role in the removal of excess cysteine and in the synthesis of taurine. Hepatic taurine synthesis is largely restricted by the low availability of cysteinesulfinate as substrate for cysteinesulfinate decarboxylase, and taurine production is increased when cysteinesulfinate increases in response to an increase in the hepatic cysteine concentration and the associated increase in cysteine dioxygenase activity. The upregulation of cysteine dioxygenase in the presence of cysteine is a consequence of diminished ubiquitination of cysteine dioxygenase and a slower rate of degradation by the 26S proteasome.     

Mechanisms of Adenosine Release in the Developing and Adult Mouse Hippocampus

Adenosine is a neuromodulator known to inhibit the synaptic release of neurotransmitters, e.g., glutamate, and to hyperpolarize postsynaptic neurons. The release of adenosine is markedly enhanced under ischemic conditions. It may then act as an endogenous neuroprotectant against cerebral ischemia and excitotoxic neuronal damage. The mechanisms by which adenosine is released from nervous tissue are not fully known, particularly in the immature brain. We now characterized the release of [³H]adenosine from hippocampal slices from developing (7-day-old) and adult (3-month-old) mice using a superfusion system. The properties of the release differed only partially in the immature and mature hippocampus. The K⁺-evoked release was Ca²⁺ and Na⁺ dependent. Anion channels were also involved. Ionotropic glutamate receptor agonists potentiated the release in a receptor-mediated manner. Activation of metabotropic glutamate receptors enhanced the release in developing mice, with group II receptors alone being effective. The evoked adenosine release apparently provides neuroprotective effects against excitotoxicity under cell-damaging conditions. Taurine had no effect on adenosine release in adult mice, but depressed the release concentration dependently in the immature hippocampus.     

Thermodynamics of yeast cell osmoregulation: Passive mechanisms

The response of yeast cells to osmotic pressure variations of the medium were studied through the kinetics of cell-volume modifications corresponding to the mass transfer of water and solutes. Osmotic variations were made by modification of the concentration of an external binary solution (polyol/water) without nutritive components. Two phases were distinguished in the thermodynamic response. A transient phase following an osmotic shift, which is characterised by rapid water transfer across the cell membrane and whose kinetics determine cell viability; then, a steady-state phase is reached when the cell volume becomes quasi-constant. The response of the cell during the transient phase depends on the level of the osmotic stress, and hence of the osmotic pressure of the medium. In the range of weak osmotic pressures, the metabolism of the cell is preserved through the maintenance of the intracellular turgor pressure. On the other hand in the range of high osmotic pressures of the medium, yeast cells behave as osmometers and no further metabolism occurs.     

The Role of Taurine in the Central Nervous System and the Modulation of Intracellular Calcium Homeostasis

The effects of taurine in the mammalian nervous system are numerous and varied. There has been great difficulty in determining the specific targets of taurine action. The authors present a review of accepted taurine action and highlight recent discoveries regarding taurine and calcium homeostasis in neurons. In general there is a consensus that taurine is a powerful agent in regulating and reducing the intracellular calcium levels in neurons. After prolonged L-glutamate stimulation, neurons lose the ability to effectively regulate intracellular calcium. This condition can lead to acute swelling and lysis of the cell, or culminate in apoptosis. Under these conditions, significant amounts of taurine (mM range) are released from the excited neuron. This extracellular taurine acts to slow the influx of calcium into the cytosol through both transmembrane ion transporters and intracellular storage pools. Two specific targets of taurine action are discussed: Na⁺-Ca²⁺ exchangers, and metabotropic receptors mediating phospholipase-C.     

束缚应激对大鼠同型半胱氨酸代谢的影响

为了探讨束缚应激对大鼠血清含硫氨基酸代谢的影响,根据同型半胱氨酸(Hcy)水平,将32只雄性Wistar大鼠分为对照组(control)、束缚应激组(RS)、1%蛋氨酸组(1%Met)和1%蛋氨酸+束缚应激组(1%Met+RS)。采用高压液相色谱法检测血清中的Hcy、半胱氨酸(Cys)和还原型谷胱甘肽(GSH)含量,采用全自动氨基酸分析仪测定血清中蛋氨酸(Met)和牛磺酸(Tau)含量。结果显示,RS组大鼠血清Hcy、Cys和GSH含量随着束缚时间延长而降低,且较对照组和1%蛋氨酸组有显著性差异(p<0.05);RS组大鼠血清Met和Tau含量较对照组和1%蛋氨酸组则显著升高(p<0.05)。束缚应激可能降低血清抗氧化能力和总Hcy水平。