Evaluation of the osmoregulatory function of taurine in brain cells

Summary Homogenous primary cultures of mouse astrocytes and cortical neurons were used to clarify the role of taurine in ion and osmoregulation in the CNS. This study indicates that both neurons and glial cells have uptake systems for taurine. The cell water content does not change during loading of cells with taurine. Chemical analysis indicates that part of the accumulated taurine is metabolized and that the product(s) are stored in the cells. Extracellular taurine (1 mM) has no effect on K⁺, Na⁺, Cl^-, or Ca²⁺ movements in astrocytes. However, astrocytes loaded to a taurine content which corresponds a concentration of 60 mM (corresponds to normal mouse cortex levels) show a 50% reduction in their K⁺ accumulation by carriers and a 100% increase in Ca²⁺ turnover rates. Movements of Ca²⁺ and K⁺ are involved in neurotransmission. It appears that taurine stored in glial cells, has an important effect on ion homeostasis in the CNS and may act indirectly on neuronal excitability.     

Is there a role of taurine bromamine in inflammation? Interactive effects with nitrite and hydrogen peroxide

Objective and Design: The myeloperoxidase system of neutrophils generates chlorinating and brominating oxidants in vivo. The major haloamines of the system are taurine chloramine (TauCl) and taurine bromamine (TauBr). It has been demonstrated in vitro that TauCl exerts both antiinflammatory and anti-bacterial properties. Much less is known about TauBr. The present study was conducted to compare bactericidal and immunoregulatory capacity of TauBr with that of the major chlorinating oxidants: HOCl and TauCl. Moreover, the effect of nitrites and H₂O₂ on TauBr activity was investigated.Materials: TauBr was prepared by reaction of HOBr with taurine. The reaction was monitored by UV absorption spectra.Methods: Bactericidal activity of TauBr, TauCl and HOCl was tested by incubation of E. coli with the compounds and determined by the pour-plate method. To test the anti-inflammatory activity the compounds were incubated with LPS and IFN- stimulated murine peritoneal macrophages. The production of following mediators was measured: nitrites by Griess reaction; TNF-, IL-6, IL-10, IL-12p40 using capture ELISA. In some experiments the compounds were incubated with either nitrites or H₂O₂.Results: In our experimental set-up TauBr and HOCl exerted strong bactericidal effects on E. coli (MBC = 110 M and 8 M, respectively), while TauCl (< 1000 M) did not kill test bacteria. However, both, TauBr and TauCl, at noncytotoxic concentrations (< 300 M) inhibited the cytokine and nitric oxide production by macrophages. H₂O₂ completely abolished the biological activities of TauBr but not those of TauCl. Nitrites did not affect any activity of TauBr or TauCl while they diminished the HOCl^– mediated bacterial killing.Conclusion: TauBr, despite very low concentration of Br^– in body fluids, may support TauCl and HOCl in the regulation of inflammatory response and in killing of bacteria by neutrophils. However, TauBr activity in vivo will depend on the presence of H₂O₂ and possible other mediators of inflammation which can compete with target molecules for TauBr.Received 16 August 2004; returned for revision 16 September 2004; accepted by A. Falus 13 October 2004     

Can energy drinks reduce the depressor effect of ethanol? An experimental study in mice

Although the popularization of the combined use of alcoholic beverages and energy drinks (ED) containing caffeine, taurine and other substances has increased, there are no controlled experimental studies on the effects of ED alone or combined with ethanol. This work aimed at evaluating the effects of different doses of ED combined or not with ethanol, on the locomotor activity of Swiss mice. The administration of 3.57, 10.71 or 17.86 ml/kg of ED alone increased the locomotor activity of the animals in relation to a control group. Low doses of ethanol (0.5, 1.0 and 1.5 g/kg) alone or in combination with 10.71 ml/kg of ED did not affect their locomotor activity. However, the reduction of activity observed after 2.5 g/kg of ethanol was antagonized by 10.71 ml/kg of ED. Further studies on the mechanisms of this interaction are still needed.     

Hyposmolarity-activated fluxes of taurine in astrocytes are mediated by diffusion

In order to obtain information about the mechanism responsible for swelling associated taurine release in astrocytes, the kinetics of taurine uptake in cultured astrocytes from mouse cerebral cortex was studied under isosmotic and hyposmotic (50% osmolarity) conditions. It was found that the V_max for the high affinity component of taurine uptake was unaffected by exposure of the astrocytes to hyposmotic conditions and that the K_m value was somewhat increased. Contrary to V_max, the non-saturable component of the uptake was greatly increased (2.5-fold) after exposure of the cells to hyposmotic media leading to cell swelling. In addition to the kinetic characterization of taurine uptake the actual intracellular taurine content after incubation (15 min) in isosmotic or hyposmotic media with different taurine concentrations (0–100 mM) under Na⁺-free conditions was determined. At taurine concentrations < 30 mM corresponding to the intracellular content in cells not exposed to taurine, exposure to hyposmotic media led to a decrease in the intracellular taurine content. At higher external taurine concentrations (> 30 mM) the intracellular taurine contents were dramatically increased after exposure to hyposmotic conditions. The increase in intracellular taurine seen under hyposmotic conditions at 100 mM external taurine could be significantly reduced by 100 μM DIDS (4,4′-diisothiocyanatostilbene-2,2′-disulfonate). Altogether these results suggest that a diffusional process rather than the high affinity taurine carrier is involved in the swelling induced increase in astrocytic taurine influx and efflux.     

Hypotonicity stimulates translocation of ICln in neonatal rat cardiac myocytes

 Cell volume expansion stimulates the efflux of solutes, including the amino acid taurine, to accomplish a regulatory volume decrease (RVD). One protein that may play a role in taurine efflux is the cytosolic protein ICln. In rat neonatal cardiac myocytes under isotonic conditions, ICln is found predominantly (greater than 90%) in the cytosol. However, after cell volume expansion by exposure to hypotonic medium, ICln rapidly translocates to the particulate fraction (the Triton X-114-insoluble fraction). After 2 min in hypotonic medium the percentage of ICln in the particulate fraction increases to 30%, 46% at 5 min, 40% at 10 min, and 25% at 30 min. The time course of this response is similar to that of hypotonicity-stimulated taurine efflux. Hypotonicity-stimulated taurine efflux as well as ICln translocation parallel the reduction in medium osmolarity. As osmolarity decreases, taurine efflux and ICln movement increase. The movement of ICln from the particulate back to the cytosolic fraction is accelerated when volume-expanded cells are returned to isotonic medium. When ICln is analyzed under non-denaturing conditions, a dimer is detected in the particulate fraction of volume-expanded cells, along with the monomer. This dimer is not detected in the cytosol. Treatment of the particulate fraction from volume-expanded cells with the lyotropic agent KSCN caused release of ICln but not Na-K-ATPase into the soluble fraction, indicating that translocated ICln associates with membranes in the particulate fraction rather than inserting into them. Received: 31 October 1997 / Received after revision and accepted: 23 March 1998     

牛磺酸对培养乳鼠心肌细胞缺氧坏死的保护作用

目的　观察牛磺酸 (Tau)对缺氧引起的心肌细胞坏死有无直接保护作用。方法　将培养心肌细胞分为正常对照、Tau对照缺氧 Tau和缺氧 4个组。测定培养细胞上清液中肌酸磷酸激酶 (CPK)活性 ,用原子吸收法测定细胞内钙、镁含量 ,Annexin V- FITC/ PI双染流式细胞术和台盼蓝染色镜检检测坏死细胞。结果　 Tau可使缺氧时培养细胞上清液中CPK活性降低 30 % ,坏死细胞减少大约 2 0 %。减少细胞内钙超载和镁丢失。结论　 Tau对缺氧导致的心肌细胞坏死有直接保护作用 ,此作用可能与减少细胞内钙超载和镁丢失有关。     

自发性高血压大鼠应用卡托普利加左旋精氨酸、牛磺酸的实验研究

目的：为研究左旋精氨酸、牛磺酸、卡托普利三药合用对自发性高血压大鼠的血压、血脂以及同同型半胱氨酸的影响。方法：用酶法测血脂,用高效液相色谱法测血浆HCY,在大鼠清醒状态下,测鼠尾的尾动脉收缩压,观察两组自发性高血压大鼠（卡托普利单用组,左旋精氨酸＋牛磺酸＋卡托普利三药合用组）在用药前后各指标的变化。结果：①经过四周药物治疗,合用组血压下隆比卡托普利组明显（P＜0.01）。②卡托普利组血脂无降低（P＞0.05）。合用组TC和TG均降低,（P＜0.005)。③两组HCY均下降。用药前,大鼠血压高低与血浆HCY的浓度无相关性（P＞0.05）,用药后,血压的下降与血浆HCY浓度的变化无相关性（P＞0.05）。结论：①卡托普利与有氨酸、牛磺酸合用对血压、血脂的控制比单用卡托普利。②血压的下降与同型半胱氨酸的下降无相关性（P＞0.05）。     

左旋精氨酸、牛磺酸及卡托普利对自发性高血压大鼠血压相关因素的影响

目的：研究左旋精氨酸、牛磺酸、卡托普利单用及合用对自发性高血压大鼠的血压以及血神经肽Y、血脂水平的影响。方法：①用MRB－ⅢA型血压记录仪（上海第二医科大学高血压研究所）,在大鼠清醒状态下,测鼠尾的尾动脉收缩压。②用酶法测定血清胆固醇（TC）、甘油三酯（TG）。③用^125I标记法和放射免疫法测血浆神经肽Y。结果：①经过四周药物治疗,左旋精氨酸且（L-arg)、牛磺酸组（Tau）血压均无变化（P＞0．05）。卡托普利组（Cap )、三药合用组（L－arg Tau Cap)血压均下降（P＜0．0005）,L－arg Tau Cap组,血压下降比卡托普利组明显（P＜0．01）。②经过四周药物治疗,牛磺酸组TC降低,TG无变化。L－arg Tau Cap组TC和TG均降低,左旋精氨酸组、卡托普利组TC和TG均无变化（P＞0．05）。③经过四周药物治疗,左旋精氨酸组、牛磺酸组NPY无变化（P＞0．05）。卡托普利组、L－arg Tau Cap 组NPY下降。用药前后,四组SHR大鼠血压高低与血浆神经肽Y的浓度均呈正相关（P＜0．05）。结论：①四组大鼠治疗后,左旋精氨酸、牛磺酸组血压换变化;卡托普利组和合用组均出现血压降低,合用组降压效果经弹卡托普利明显。②牛磺酸治疗组血清胆固醇降低;三种药物合用组血清胆固醇和甘油三酯的降低。左旋精氨酸组、卡托普利组血脂无变化。③自发 性高血压大鼠的血压变化与血浆神经肽Y浓度的变化呈正相关,神经肽Y可能参与了高血压的发生发展。     

Investigations into the effects of various hepatotoxic compounds on urinary and liver taurine levels in rats

The effect of various hepatotoxicants on urinary taurine and urinary creatine has been studied in the rat. Several hepatotoxic agents, carbon tetrachloride, thioacetamide, galactosamine and allyl alcohol which all caused hepatic necrosis (sometimes accompanied by steatosis), resulted in a rise in urinary taurine and in some cases creatine, when administered to rats. Ethionine and hydrazine also raised urinary taurine but caused only steatosis and did not raise urinary creatine. Therefore urinary taurine and possibly creatine may be useful markers of liver injury and dysfunction. Liver taurine levels were also affected by some of the hepatotoxicants but in those cases where there was a rise in urinary taurine this could not be accounted for by the loss in liver taurine. It is suggested that the increase in urinary taurine is partly due to changes in protein synthesis and hence in sulphur amino acid metabolism caused by hepatotoxic agents. However, bromobenzene did not increase urinary taurine and-naphthylisothiocyanate and lithocholate caused reduced levels. It is suggested that this lack of increase in urinary taurine may be due to depletion of glutathione or interference with the biliary system.