Effects of taurine in glucose and taurine administration

Summary. Taurine has several biological processes such as hypoglycemic action, antioxidation, detoxification, etc. To assess the effect of taurine administration on the guinea pigs with hyperglycemia, blood glucose, C-peptide levels together with morphologic alterations in the pancreatic ultrastructure were investigated in terms of hypoglycemic action and malondialdehyde and total sulfhydryl group levels with regard to oxidation-antioxidation relation. Animals were divided into four groups of six. Glucose supplementation group was administrated a single dose of glucose (400mg/kg, i.p.) injection. Glucose and taurine supplementation group was administrated glucose treatment (a single dose, 400mg/kg, i.p.) following taurine (a single dose, 200mg/kg, i.p.). Taurine and glucose supplementation group was administered taurine treatment (a single dose, 200mg/kg, i.p.) following glucose treatment (a single dose, 400mg/kg, i.p.). Control animals received no treatment. Blood samples were collected at the end of the experiments for the determination of glucose, C-peptide (indicator of insulin secretion), lipid peroxidation (thiobarbituric acid reactive substances), and total sulfhydryl groups levels. Pancreatic tissue samples were then collected and processed for transmission electron microscopy. The findings showed that glucose supplementation following taurine administration significantly decreased blood glucose level by increasing C-peptide level and the pancreatic secretion stimulated morphologically and insignificantly changed thiobarbituric acid reactive substances and total sulfhydryl group levels. These observations suggest that taurine administration may be useful in hyperglycemia because of its hypoglycemic and protective effects.     

Physical and structural properties of taurine and taurine analogues

Summary In a variety of mammalian species it has been established that taurine is a necessary component of the visual system, however, the exact mechanism(s) as to the function of taurine is(are) elusive. Additionally, taurine is speculated to be a membrane stabilizer by interacting with phospholipids and a regulator of protein phosphorylation. Therefore the inhibition by taurine and taurine analogues of the phosphorylation of an 20 kDa protein present in the mitochondrial fraction of the rat retina has been investigated using computational methods. Correlations between molecular weight, molecular volume, and calculated pKa values vs. IC₅₀ values are reported. These data appear to support the hypotheses according to Lombardini and Props that the inhibition of the phosphorylation of an 20kDa protein by taurine and taurine analogues is dependent on (i) the critical distance between the nitrogen and sulfur atoms in the taurine moiety (S-C-C-N) of the analogue; (ii) the environment of the nitrogen atom in the taurine analogue (saturated ring vs. unsaturated ring); and (iii) the placement of both the sulfur and nitrogen atoms not being present simultaneously in the ring structure. Using computational methods we present results that support hypotheses (i) and (ii).     

Net taurine transport and its inhibition by a taurine antagonist

P₂-fractions were isolated from rat brain, and used to study net taurine transport. The fractions were incubated in increasing concentrations of [³H]taurine and the intraterminal concentration measured by liquid scintillation and amino acid analysis. The membrane potential of the isolated fractions was estimated using⁸⁶Rb⁺ as a marker for intracellular K⁺. Taurine was synthesized in the P₂-fraction when incubated in taurine free medium. At external taurine concentrations below 370 M a significant amount of the endogenous taurine was released to the incubation medium. Net taurine uptake into the P₂-fraction was achieved at external taurine concentrations exceeding 370 M. The taurine antagonist 6-aminomethyl-3-methyl-4H, 1, 2, 4-benzothiadiazine-1, 1-dioxide (TAG) competitively inhibited taurine and [³H]taurine transport into the P₂-fraction. As the external concentration of taurine was increased, the accumulation of⁸⁶Rb⁺ into the P₂-fraction was facilitated. This indicated an increasing hyperpolarization of the neuronal membrane as taurine transport shifted from release towards uptake. TAG reduced the hyperpolarization that paralleled taurine accumulation, in a dose dependent manner. Our results indicate that relatively low transmembranal gradients of taurine may be maintained by an electrogenic taurine transporter having a large transport capacity. Such a transporter may well serve the needs of osmotic regulation, i.e. to transport large amounts of taurine in any direction across the neuronal membrane.     

Membrane-modifying effect of taurine

The effect of taurine on membrane-associated processes was studied in rat erythrocytes and peritoneal mast cells. EPR with a spin probe 5-DS revealed a significant decrease in the order parameter S of membrane phospholipid acyl chains in vitro after incubation of erythrocytes with taurine (10 mM, 1 h). Increased susceptibility of the erythrocyte membrane to peroxide-induced lysis was also observed. These effects suggested decreased membrane microviscosity resulting from less dense packing of the phospholipids. The differential effects of taurine on stimulated Ca-dependent functional activity of peritoneal mast cells (histamine liberation) upon different ways of administration (oral, intraperitoneal, or intramuscular) suggest an indirect and complex mechanism of taurine action in the organism.     

Comparison of taurine chloramine and taurine bromamine effects on rheumatoid arthritis synoviocytes

Summary. Fibroblast-like synoviocytes (FLS) participate in rheumatoid arthritis (RA) chronic synovitis by producing pro-inflammatory cytokines (IL-6, IL-8), growth factors (VEGF) and other inflammatory mediators (PGE₂, NO). We have previously reported that Tau-Cl, generated by neutrophils, inhibits in vitro some of these pathogenic RA FLS functions. Taurine bromamine (Tau-Br) originates from eosinophils and neutrophils, and its immunoregulatory activities are poorly known. Therefore, we investigated the effects of Tau-Br on RA FLS functions and compared it to Tau-Cl anti-inflammatory action. When applied at noncytotoxic concentrations: (i) Tau-Br inhibited IL-6 and PGE₂ production with potency similar to Tau-Cl (IC₅₀ ≈ 250 μM), (ii) Tau-Br failed to affect VEGF and IL-8 synthesis, while Tau-Cl exerted inhibitory effect (IC₅₀ ≈ 400 μM), (iii) none of these compounds affected NO generation and iNOS expression. Thus, Tau-Cl is more effective than Tau-Br in normalization of pro-inflammatory RA FLS functions.     

Physiological significance of taurine and the taurine transporter in intestinal epithelial cells

Summary. Taurine transport in human intestinal epithelial Caco-2 cells was down-regulated by culturing the cells in taurine-containing media and was up-regulated in a taurine-free medium. This adaptive regulation was associated with changes in both the Vmax and Km values of taurine transport. A change in the mRNA level of the taurine transporter (TAUT) in this regulation was also observed. The presence of such a regulatory mechanism for maintaining the intracellular taurine content at a certain level suggests that taurine plays an important role in the intestinal cell functions. The intracellular taurine content was increased when Caco-2 cells were exposed to a hypertonic stress. TAUT was up-regulated via the increased expression of TAUT mRNA in the hypertonic cells, suggesting that taurine serves as an osmolyte and protects the cells from osmotic stress. Similar up-regulation of TAUT was observed in the small intestine of water-deprived rats. Received January 25, 2000/Accepted January 31, 2000     

高糖对培养大鼠心肌细胞牛磺酸转运的影响及其可能机制

目的：观察不同浓度葡萄糖对细胞牛磺酸(taurine)转运功能的影响。方法：在培养的大鼠心肌细胞上,用^3H标记的牛磺酸测定细胞牛磺酸转运和竞争性定量RTPCR测定细胞牛磺酸转运体(TAUT)mRNA含量。结果：不同浓度葡萄糖(10～30mmol/L)孵育,抑制细胞^3H-牛磺酸转运,呈时间依赖性。与对照组比较,高糖(20mmol／L和30mmol／L)使心肌细胞牛磺酸摄入量显著减少,其^3H-牛磺酸转运的最大速率(Vmax)减少,心肌细胞TAUTmRNA含量较对照组减少。结论：高糖抑制心肌细胞牛磺酸转运,这与TAUT的牛磺酸结合位点减少和TAUT基因转录水平下调有关。     

Effects of taurine and a taurine antagonist on some respiratory and cardiovascuar parameters

Respiratory performance, heart rate and blood pressure were studied in halothane anesthetized rats after administration of taurine and the putative taurine antagonist 6-aminomethyl-3-methyl-4H-1,2,4-benzothiadiazine-1, 1-dioxide hydrochloride (TAG). Intracerebroventricular (i.c.v.) taurine depressed ventilation due to decreased inspiratory neural drive and depression of respiratory timing mechanisms. I.c.v. administration of 1–100 μg TAG caused no changes in the respiratory adn circulatory parameters studied except at the highest dose interval where respiratory frequency and minute ventilation were depressed. The respiratory depression induced by taurine (0.2 mg) or β-alanine (1 mg) was antagonized by administration of TAG (100 μg). However, TAG did not antagonize the respiratory effects induced by i.c.v. glycine or γ-aminobutyric acid (GABA) in equipotent respiratory depressant doses. The decline in inspiratory neural drive as well as in “respiratory timing” after i.c.v. taurine was restituted toward control values by TAG. The hypotension and bradycardia induced by taurine were also antagonized by TAG. It is concluded that TAG seems to antagonize the depressant action of taurine and β-alanine but not of GABA and glycine on respiratory performance. TAG might also possess some partial agonist activity in higher doses.     

A simple assay of taurine concentrations in food and biological samples using taurine dioxygenase

Taurine demonstrates various physiological functions and pharmacological actions. A successful application of taurine dioxygenase (EC 1.14.11.17) for taurine determination is described. The gene encoding taurine dioxygenase was cloned from Escherichia coli strain K-12, and the enzyme was used to determine taurine in commercially available beverages and some biological samples. The measured values obtained using the current method are close to the declared values with the precolumn derivatization ultra-performance liquid chromatography (UPLC) procedure. Taurine dioxygenase can be used for taurine determination in food control, biological research, and diagnoses based on urinary taurine concentration.     

Cardiac taurine levels during endotoxemia

Three hours after dogs were given an intravenous injection of Escherichia coli endotoxin significant decreases in cardiac taurine levels were observed in the apex and epicardial regions of the right ventricle and in all regions sampled from the left ventricle. A decrease in taurine was seen in all regions of the heart (including the atria) by 90 min after endotoxin treatment but the results were not statistically significant. Echocardiography and left ventricular cannulation were used in a separate group to confirm that the dose of endotoxin used was adequate to produce depression of cardiac output and force of contraction.     

The use of taurine analogues to investigate taurine functions and their potential therapeutic applications

Summary.  Despite the multitude of evidence for the beneficial effects of taurine supplementation in a variety of disease, the underlying modifying action of taurine with respect to either molecular or biochemical mechanisms is almost totally unknown. We have assessed the development of taurine analogues, particularly where there has been substitution at the suphonate or amine group. Such substitutions allow the investigator to probe the relationship between structure and function of the taurine molecule. In addition such studies should help to ascertain taurine's point of interaction with the effector molecule. These results will prepare the way for the development of the second generation of taurine analogues. Received January 2, 2002 Accepted January 28, 2002 Published online August 30, 2002 Acknowledgements This research has been funded by the COST Chemistry programmes COST D8 “Chemistry of Metals in Medicine” and D-13 “New Molecules for Human Health Care”. All of the authors are members of the Working Group D13/0011/00 “Investigation of mechanisms underlying the pharmacological actions of taurine upon cell apoptosis and calcium homeostasis”. Authors' address: Dr. R.J. Ward, Unite de Biochimie, Catholic Universite de Louvain, Place Louis Pasteur 1, B-1348 Louvain-la-Neuve, Belgium, E-mail: ward@bioc.ucl.ac.be     

Effect of selenium deficiency on tissue taurine concentration and urinary taurine excretion in the rat

The purpose of this study was to determine the effect of selenium deficiency on tissue taurine levels and urinary taurine excretion. Weanling male Sprague-Dawley rats were fed selenium-deficient or selenium-adequate diets for 20 weeks. As selenium deficiency developed, urinary taurine excretion increased in selenium-deficient rats compared to controls. At 12 weeks, the selenium-deficient rats excreted 1.7-fold more taurine than control rats. At the same time plasma glutathione peroxidase was 1.2% of control and plasma glutathione was 226% of control. At 20 weeks, renal taurine was decreased but renal glutathione was increased in selenium-deficient rats compared to controls. Feeding the experimental diet for 6 weeks without methionine supplementation caused a fall in urinary taurine excretion. However, there was no difference between selenium-deficient and control rats. These results indicate that selenium deficiency affects renal handling of taurine in the rat when dietary sulfur amino acids are not restricted.     

Volume-sensitive taurine transport in fish erythrocytes

Summary Taurine plays an important role in cell volume regulation in both vertebrates and invertebrates. Erythrocytes from two euryhaline fish species, the eel (Anguilla japonica) and the starry flounder (Platichthys stellatus) were found to contain high intracellular concentrations of this amino acid ( 30 mmol per liter of cell water). Kinetic studies established that the cells possessed a saturable high-affinity Na⁺-dependent -amino-acid transport system which also required Cl^– for activity (apparentK _m (taurine) 75 and 80 m;V _max 0.85 and 0.29 mol/g Hb per hr for eel (20°C) and flounder cells (10°C), respectively. This -system operated with an apparent Na⁺/Cl^–/taurine coupling ratio of 211. A reduction in extracellular osmolarity, leading to an increase in cell volume, reversibly decreased the activity of the transporter. In contrast, low medium osmolarity stimulated the activity of a Na⁺-independent nonsaturable transport route selective for taurine, -amino-n-butyric acid and small neutral amino acids, producing a net efflux of taurine from the cells. Neither component of taurine transport was detected in human erythrocytes. It is suggested that these functionally distinct transport routes participate in the osmotic regulation of intracellular taurine levels and hence contribute to the homeostatic regulation of cell volume. Volume-induced increases in Na⁺-independent taurine transport activity were suppressed by noradrenaline and 8-bromoadenosine-3, 5-cyclic monophosphate, but unaffected by the anticalmodulin drug, pimozide.     

The metabolism of taurine to isethionate

The biosynthesis of isethionate from taurine in mammalian tissue has been reexamined. In vivo metabolism of taurine to isethionate was demonstrated but it was shown that a number of acyltaurine metabolites also behave like isethionate on the conventional dual column ion-exchange chromatographic analytical system. Hydrolysis of these column effluates coupled with high-voltage electrophoresis resolves this ambiguity. In vivo formation of isethionate from taurine in mammals seems to occur from gut microorganism metabolism since: (a) germ-free mice could not convert taurine to isethionate, (b) gut anaerobes were able to metabolize taurine, (c) in vitro rat and mouse tissue failed to metabolize taurine to isethionate. These findings are in conflict with earlier reports.