The cytoprotective role of taurine in exercise-induced muscle injury

Summary.  Intense exercise is thought to increase oxidative stress and damage muscle tissue. Taurine is present in high concentration in skeletal muscle and may play a role in cellular defenses against free radical-mediated damage. The aim of this study was to determine if manipulating muscle levels of taurine would alter markers of free radical damage after exercise-induced injury. Adult male Sprague-Dawley rats were supplemented via the drinking water with either 3% (w/v) taurine (n = 10) or the competitive taurine transport inhibitor, β-alanine (n = 10), for one month. Controls (n = 20) drank tap water containing 0.02% taurine and all rats were placed on a taurine free diet. All the rats except one group of sedentary controls (n = 10) were subjected to 90 minutes of downhill treadmill running. Markers of cellular injury and free radical damage were determined along with tissue amino acid content. The 3% taurine treatment raised plasma levels about 2-fold and 3% β-alanine reduced plasma taurine levels about 50%. Taurine supplementation (TS) significantly increased plasma glutamate levels in exercised rats. Exercise reduced plasma methionine levels and taurine prevented its decline. Taurine supplementation increased muscle taurine content significantly in all muscles except the soleus. β-alanine decreased muscle taurine content about 50% in all the muscles examined. Lipid peroxidation (TBARS) was significantly increased by exercise in the extensor digitorium longus (EDL) and gastrocnemius (GAST) muscles. Both taurine and β-alanine completely blocked the increase in TBARs in the EDL, but had no effect in the GAST. Muscle content of the cytosolic enzyme, lactate dehydrogenase (LDH) was significantly decreased by exercise in the GAST muscle and this effect was attenuated by both taurine and β-alanine. Muscle myeloperoxidase (MPO) activity was significantly elevated in the gastrocnemius muscle, but diet had no effect. MPO activity was significantly increased by exercise in the liver and both taurine and β-alanine blocked this effect. There was no effect of either exercise or the diets on MPO activity in the lung or spleen. Running performance as assessed by a subjective rating scale was improved by taurine supplementation and there was a significant loss in body weight in the β-alanine-treated rats 24 hours after exercise. In summary, taurine supplementation or taurine depletion had measurable cytoprotective actions to attenuate exercise-induced injury. Received October 22, 2001 Accepted February 1, 2002     

The effect of taurine on renal ischemia/reperfusion injury

Summary. Ischemia-reperfusion (I/R) injury is one of the most common causes of renal dysfunction. Taurine is an endogenous antioxidant and a membrane-stabilizing, intracellular, free beta-amino acid. It has been demonstrated to have protective effects against I/R injuries to tissues other than kidney. The aim of this study was to determine whether taurine has a beneficial role in renal I/R injury. Forty Wistar-Albino rats were allocated into four groups as follows: sham, taurine, I/R, and I/R + taurine. Taurine 7.5 mg/kg was given intra-peritoneally to rats in the groups taurine and I/R + taurine. Renal I/R was achieved by occluding the renal arteries bilaterally for 40 min, followed by 6 h of reperfusion. Immediately thereafter, blood was drawn and tissue samples were harvested to measure 1) serum levels of BUN and creatinine; 2) serum and/or tissue levels of malondialdehyde (MDA), glutathione (GSH), glucose 6-phosphate dehydrogenase (G-6PD), 6-phosphogluconate dehydrogenase (6-PGD) and glutathione reductase (GSH-red); 3) renal morphology; and 4) immunohistochemical staining for P-selectin. Taurine administration reduced I/R-induced increases in serum BUN and creatinine, and serum and tissue MDA levels (p < 0.05). Additionally, taurine lessened the reductions in serum and tissue glutathione levels secondary to I/R (p < 0.05). Taurine also attenuated histopathologic evidence of renal injury, and reduced I/R-induced P-selectin immunoreactivity (p < 0.05). Overall, then, taurine administration appears to reduce the injurious effects of I/R on kidney.     

Indispensable amino acid concentrations decrease in tissues of stomachless fish,common carp in response to free amino acid- or peptide-based diets

Summary. The premise that free amino acid or dipeptide based diets will resolve the nutritional inadequacy of formulated feeds for larval and juvenile fish and improve utilization of nitrogen in comparison to protein-based diets was tested in stomachless fish, common carp (Cyprinus carpio L.) larvae. We examined the postprandial whole body free amino acid (FAA) pool in fish that were offered a FAA mixture based diet for the duration of 2 or 4 weeks. We found that the total amount and all indispensable amino acids concentrations in the whole body decreased after a meal. We then fed juvenile carp with dietary amino acids provided in the FAA, dipeptide (PP), or protein (live feed organisms; brine shrimp Artemia salina nauplii, AS) forms. Histidine concentrations in the whole fish body increased in all dietary groups after feeding whereas all other indispensable amino acids decreased in FAA and PP groups in comparison to the AS group. Taurine appears to be the major osmotic pressure balancing free amino acid in larval freshwater fish which may indicate a conditional requirement. We present the first evidence in larval fish that in response to synthetic FAA and PP diets, the whole body indispensable free AA concentrations decreased after feeding. This study shows that amino acids given entirely as FAA or PP cannot sustain stomachless larval fish growth, and may result in depletion of body indispensable AA and most of dispensable AA. The understanding of these responses will determine necessary changes in diet formulations that prevent accelerated excretion of amino acids without protein synthesis.     

Beneficial effects of taurine on serum lipids in overweight or obese non-diabetic subjects

Summary. Taurine has beneficial effects on lipid metabolism in experimental animals fed with high-cholesterol or high fat diets. Whether taurine benefits lipid metabolism in humans has rarely been investigated. The aim of this study was to evaluate the effects of taurine on serum lipids in overweight or obese young adults. Thirty college students (age: 20.3±1.7 years) with a body mass index (BMI) 25.0kg/m², and with no evidence of diabetes mellitus were selected and assigned to either the taurine group (n=15) or the placebo group (n=15) by double-blind randomization. Taurine 3g/day or placebo was taken orally for 7 weeks. Triacylglycerol (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and plasma glucose were measured before and after supplementation. The atherogenic index (AI) was calculated as (TC–HDL-C)/HDL-C. There were no differences in any baseline parameter between the two groups. Taurine supplementation decreased TG and AI significantly. Body weight also reduced significantly in the taurine group. These results suggest that taurine produces a beneficial effect on lipid metabolism and may have an important role in cardiovascular disease prevention in overweight or obese subjects.     

Observations on the relationship between the extracellular changes of taurine and glutamate during cortical spreading depression, during ischemia, and within the area surrounding a thrombotic infarct

Summary. Taurine and glutamate were monitored by microdialysis technique during various cerebral insults: a. Application of K⁺ triggered a cortical spreading depression (CSD). Taurine and glutamate increased concomitantly but recovery of glutamate was faster than that of taurine. b. Application of NMDA induced also CSD but only taurine increased. c. Induction of an infarct triggered repetitive CSDs. Taurine increased rapidly whereas glutamate rose slowly starting with some delay. d. After induction of ischemia, taurine and glutamate increased after onset of depolarisation. The increase of glutamate occurred late after a small, transient increase in parallel with the depolarisation. These data suggest a close functional relationship between the changes of both amino acids. Therefore, they should be monitored together especially in clinical settings: during excitation, only taurine will increase; during overexcitation, taurine will also increase but to a higher maximum followed by a moderate rise of glutamate; after energy failure, taurine will accumulate to its highest level followed by a continuous rise of glutamate. Received January 25, 2000/Accepted January 31, 2000     

Taurine release in mouse brain stem slices under cell-damaging conditions

Summary. Taurine has been thought to be essential for the development and survival of neural cells and to protect them under cell-damaging conditions. In the brain stem taurine regulates many vital functions, including cardiovascular control and arterial blood pressure. We have recently characterized the release of taurine in the adult and developing brain stem under normal conditions. Now we studied the properties of preloaded [³H]taurine release under various cell-damaging conditions (hypoxia, hypoglycemia, ischemia, the presence of metabolic poisons and free radicals) in slices prepared from the mouse brain stem from developing (7-day-old) and young adult (3-month-old) mice, using a superfusion system. Taurine release was greatly enhanced under these cell-damaging conditions, the only exception being the presence of free radicals in both age groups. The ischemia-induced release was characterized to consist of both Ca²⁺-dependent and -independent components. Moreover, the release was mediated by Na⁺-, Cl⁻-dependent transporters operating outwards, particularly in the immature brain stem. Cl⁻ channel antagonists reduced the release at both ages, indicating that a part of the release occurs through ion channels, and protein kinase C appeared to be involved. The release was also modulated by cyclic GMP second messenger systems, since inhibitors of soluble guanylyl cyclase and phosphodiesterases suppressed ischemic taurine release. The inhibition of phospholipases also reduced taurine release at both ages. This ischemia-induced taurine release could constitute an important mechanism against excitotoxicity, protecting the brain stem under cell-damaging conditions.     

Interaction between the actions of taurine and angiotensin II

Summary. The amino acid, taurine, is an important nutrient found in very high concentration in excitable tissue. Cellular depletion of taurine has been linked to developmental defects, retinal damage, immundeficiency, impaired cellular growth and the development of a cardiomyopathy. These findings have encouraged the use of taurine in infant formula, nutritional supplements and energy promoting drinks. Nonetheless, the use of taurine as a drug to treat specific diseases has been limited. One disease that responds favorably to taurine therapy is congestive heart failure. In this review, we discuss three mechanisms that might underlie the beneficial effect of taurine in heart failure. First, taurine promotes natriuresis and diuresis, presumably through its osmoregulatory activity in the kidney, its modulation of atrial natriuretic factor secretion and its putative regulation of vasopressin release. However, it remains to be determined whether taurine treatment promotes salt and water excretion in humans with heart failure. Second, taurine mediates a modest positive inotropic effect by regulating [Na⁺]_i and Na⁺/Ca²⁺ exchanger flux. Although this effect of taurine has not been examined in human tissue, it is significant that it bypasses the major calcium transport defects found in the failing human heart. Third, taurine attenuates the actions of angiotensin II on Ca²⁺ transport, protein synthesis and angiotensin II signaling. Through this mechanism taurine would be expected to minimize many of the adverse actions of angiotensin II, including the induction of cardiac hypertrophy, volume overload and myocardial remodeling. Since the ACE inhibitors are the mainstay in the treatment of congestive heart failure, this action of taurine is probably very important. Received November 10, 1998, Accepted May 19, 1999     

Diuretic potential of energy drinks

Summary. Recent literature suggests that both caffeine and taurine can induce diuresis and natriuresis in rat and man. Although they act via different cellular mechanisms, their diuretic actions might be additive. This is of considerable interest, as several commercially available energy drinks contain both substances. In this study we examined the possible diuretic effects of caffeine and taurine in a cross-over-design in which 12 healthy male volunteers received each of 4 different test drinks (750 ml of energy drink containing 240 mg caffeine and 3 g taurine, the three other test drinks either lacked caffeine, taurine or both) after restraining from fluids for 12 h. Mixed model analyses demonstrated that urinary output and natriuresis were significantly increased by caffeine (mean differences 243 ml and 27 mmol; both p < 0.001) and that there were no such effects of taurine (mean differences 59 ml and −4 mmol). Additionally, urinary osmolarity at baseline was significantly related to the urinary output (p < 0.001). Urine osmolarity values at baseline and in the 6 h urine collection did not differ significantly between treatments. Taken together, our study demonstrates that diuretic and natriuretic effects of the tested energy drink were largely mediated by caffeine. Taurine played no significant role in the fluid balance in moderately dehydrated healthy young consumers. Consequently, the diuretic potential of energy drinks will not differ significantly from other caffeine containing beverages.     

Dietary taurine potentiates polychlorinated biphenyl-induced hypercholesterolemia in rats*

The effect of dietary taurine on cholesterol metabolism and the distribution of lipoprotein-cholesterol in serum of rats fed a diet containing polychlorinated biphenyls (PCB) was examined. Young male Wistar rats (60 g) were fed diets containing 0.2 g/kg diet of PCB and/or 30 g/kg diet of taurine for 15 days. The experiment was performed as the 2 (PCB) x 2 (taurine) factorial design. The addition of PCB elevated serum levels of total- and HDL-cholesterol and apolipoprotein A-I, which is a major apolipoprotein of HDL. Simultaneous supplementation of taurine with PCB amplified the increase of the serum level of total- and HDL-cholesterol. Hepatic concentrations of cholesterol and total lipids were significantly elevated by the supplementation of PCB, and taurine significantly amplified these increases caused by PCB. PCB suppressed hepatic cholesterol 7alpha-hydroxylase (CYP7A1) gene expression, and taurine induced CYP7A1 gene expression. Taurine also enhanced PCB-induced elevation of malic enzyme mRNA in the liver. These results suggest that taurine enhanced PCB-induced hyper-alpha-cholesterolemia and that taurine has a role in increasing HDL-cholesterol.     

Taurine and neural cell damage

Summary. The inhibitory amino acid taurine is an osmoregulator and neuromodulator, also exerting neuroprotective actions in neural tissue. We review now the involvement of taurine in neuron-damaging conditions, including hypoxia, hypoglycemia, ischemia, oxidative stress, and the presence of free radicals, metabolic poisons and an excess of ammonia. The brain concentration of taurine is increased in several models of ischemic injury in vivo. Cell-damaging conditions which perturb the oxidative metabolism needed for active transport across cell membranes generally reduce taurine uptake in vitro, immature brain tissue being more tolerant to the lack of oxygen. In ischemia nonsaturable diffusion increases considerably. Both basal and K⁺-stimulated release of taurine in the hippocampus in vitro is markedly enhanced under cell-damaging conditions, ischemia, free radicals and metabolic poisons being the most potent. Hypoxia, hypoglycemia, ischemia, free radicals and oxidative stress also increase the initial basal release of taurine in cerebellar granule neurons, while the release is only moderately enhanced in hypoxia and ischemia in cerebral cortical astrocytes. The taurine release induced by ischemia is for the most part Ca²⁺-independent, a Ca²⁺-dependent mechanism being discernible only in hippocampal slices from developing mice. Moreover, a considerable portion of hippocampal taurine release in ischemia is mediated by the reversal of Na⁺-dependent transporters. The enhanced release in adults may comprise a swelling-induced component through Cl⁻ channels, which is not discernible in developing mice. Excitotoxic concentrations of glutamate also potentiate taurine release in mouse hippocampal slices. The ability of ionotropic glutamate receptor agonists to evoke taurine release varies under different cell-damaging conditions, the N-methyl-D-aspartate-evoked release being clearly receptor-mediated in ischemia. Neurotoxic ammonia has been shown to provoke taurine release from different brain preparations, indicating that the ammonia-induced release may modify neuronal excitability in hyperammonic conditions. Taurine released simultaneously with an excess of excitatory amino acids in the hippocampus under ischemic and other neuron-damaging conditions may constitute an important protective mechanism against excitotoxicity, counteracting the harmful effects which lead to neuronal death. The release of taurine may prevent excitation from reaching neurotoxic levels. Received January 25, 2000/Accepted January 31, 2000     

Absorption,tissue distribution,metabolism and elimination of taurine given orally to rats

Summary. Three biodisposition studies with taurine were performed in male and female adult rats at dosages of 30 and 300 mg/kg. A single oral dose of ¹⁴C-taurine was rapidly absorbed, distributed to tissues and excreted unchanged in urine. Elimination of radioactivity from intracellular pools was slow. Pre-treatment of animals for 14 days with unlabelled taurine did not significantly affect the fate of ¹⁴C-taurine. At the higher dose there was more extensive excretion combined with a lower percentage of the dose in the carcass, indicating the possibility of saturation of the tubular reabsorption mechanism for taurine. Daily administration of unlabelled taurine for 14 days did not result in an increase in total taurine in the brain. The data indicate that exogenous taurine rapidly equilibrates with endogenous body pools and that any excess is rapidly eliminated by the kidneys.     

Taurine increases mitochondrial buffering of calcium: role in neuroprotection

Summary. We have determined the role of mitochondria in the sequestration of calcium after stimulation of cerebellar granule cells with glutamate. In addition we have evaluated the neuroprotective role of taurine in excitotoxic cell death. Mitochondrial inhibitors were used to determine the calcium buffering capacity of mitochondria, as well as how taurine regulates the ability of mitochondria to buffer intracellular calcium during glutamate depolarization and excitotoxicity. We report here that pre-treatment of cerebellar granule cells with taurine (1 mM, 24 h) significantly counteracted glutamate excitotoxicity. The neuroprotective role of taurine was mediated through regulation of cytoplasmic free calcium ([Ca²⁺] _i ), and intra-mitochondrial calcium homeostasis, as determined by fluo-3 and ⁴⁵Ca²⁺-uptake. Furthermore, the overall mitochondrial function was increased in the presence of taurine, as assessed by rhodamine accumulation into mitochondria and total cellular ATP levels. We specifically tested the hypothesis that taurine reduces glutamate excitotoxicity through both the enhancement of mitochondrial function and the regulation of intracellular (cytoplasmic and intra-mitochondrial) calcium homeostasis. The role of taurine in modulating mitochondrial calcium homeostasis could be of particular importance under pathological conditions that are characterized by excessive calcium overloads. Taurine may serve as an endogenous neuroprotective molecule against brain insults. Authors’ address: Abdeslem El Idrissi, Biology Department and Center for Developmental Neuroscience, College of Staten Island/CUNY, 6S-134 Staten Island, NY 10314, U.S.A.     

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.     

Taurine trophic modulation of goldfish retinal outgrowth and its interaction with the optic tectum

Summary. Goldfish retinal explant outgrowth in the presence of fetal calf serum is stimulated by taurine. In the absence of it, but with glucose in the medium, length of neurites is still elevated by the amino acid. Using the medium in the presence of glucose, but in the absence of fetal calf serum, we explored the effect of optic tectum medium from cultures of them coming from goldfish without crush of the optic nerve or 3, 5, 10, 14 and 20 days after crush. Retinal explants, intact or from goldfish with crush of the optic nerve 10 days prior to starting the culture, were employed in order to measure the possible effect of optic tectum media and the inter action with taurine. In other type of experiments the optic nerve was crushed 1, 2, 4, 7 and 10 days before dissection of the optic tectum, and then co-cultured with intact or 10 days post-crush retinal explants. Optic tectum media produced a time-dependent effect on outgrowth in lesioned retinas with a maximum effect around 5 days after the lesion for the corresponding optic tectum. Taurine, 4 mM, did not further affect the outgrowth in the presence of optic tectum media, but did significantly increase length of neurites either in intact or in post-lesion retinas. Co-culture of optic tectum at different days post-lesion and retinas at 10 days post-lesion increased the outgrowth around 4 days post-lesion, in a preparation resulting in mutual effects of both types of tissues. The addition of taurine in these conditions did not further increase outgrowth, rather inhibited it according to the time after lesion of optic nerve corresponding to the co-cultured optic tectum. The effect of taurine was concentration-dependent, since 0.2 mM was more effective than 2 or 4 mM in the presence of optic tectum with lesion of 2 days. These results demonstrate the time-course of the regeneration processes in the visual system of goldfish, indicating the crucial periods after crush in which the tectum could produce stimulation and later decrease or no effect on outgrowth from the retina. In addition, they are evidences of the interaction between taurine and optic tectum production of time-produced specific agents. The mechanisms underlying these effects are closely related to calcium, as it was demonstrated by the addition of extracellular or intracellular chelators to the medium, which inhibited the effects of the optic tectum and the trophic properties of taurine in this system. The inhibitor of taurine transport, guanidoethylsulfonate, also decreased the stimulatory effects of the optic tectum and of taurine, indicating an interaction of substances produced by the tectum with taurine, and an effect of taurine mediated through its entrance to the cells. Overall, retinal explants outgrowth in the absence of fetal calf serum, the interaction of agents of the optic tectum and taurine modulates outgrowth from the retina, and these effects are mediated by calcium levels and by the levels of intracellular taurine.     

Taurine promotes connective tissue growth factor (CTGF) expression in osteoblasts through the ERK signal pathway

Summary. Taurine is found in bone tissue, but its function in skeletal tissue is not fully understood. The present study was undertaken to investigate regulation of gene expression of connective tissue growth factor (CTGF), and the roles of mitogen-activated protein kinases (MAPKs) in murine osteoblast MC3T3-E1 cells treated with taurine. Western blot analysis showed taurine stimulated CTGF protein secretion in a dose- and time-dependent manner. Taurine induced activation of extracellular signal-regulated kinase (ERK), but not p38 and c-jun N-terminal Kinase (JNK), in osteoblasts. Furthermore, pretreatment of osteoblasts with the ERK inhibitor PD98059 abolished the taurine-induced CTGF production. These data indicate that taurine induces CTGF secretion in MC3T3-E1 cells mediated by the ERK pathway, and suggest that osteoblasts are direct targets of taurine.     

Taurine: Protective properties against ethanol-induced hepatic steatosis and lipid peroxidation during chronic ethanol consumption in rats

Summary Alcohol was administered chronically to female Sprague Dawley rats in a nutritionally adequate totally liquid diet for 28 days. This resulted in hepatic steatosis and lipid peroxidation. Taurine, when co-administered with alcohol, reduced the hepatic steatosis and completely prevented lipid peroxidation. The protective properties of taurine in preventing fatty liver were also demonstrated histologically. Although alcohol was found not to affect the urinary excretion of taurine (a non-invasive marker of liver damage), levels of serum and liver taurine were markedly raised in animals receiving alcohol + taurine compared to animals given taurine alone. The ethanol-inducible form of cytochrome P-450 (CYP2E1) was significantly induced by alcohol; the activity was significantly lower than controls and barely detectable in animals fed the liquid alcohol diet containing taurine. In addition, alcohol significantly increased homocysteine excretion into urine throughout the 28 day period of ethanol administration; however, taurine did not prevent this increase. There was evidence of slight cholestasis in animals treated with alcohol and alcohol + taurine, as indicated by raised serum bile acids and alkaline phosphatase (ALP). The protective effects of taurine were attributed to the potential of bile acids, especially taurine conjugated bile acids (taurocholic acid) to inhibit the activity of some microsomal enzymes (CYP2E1). Thesein vivo findings demonstrate for the first time that hepatic steatosis and lipid peroxidation, occurring as a result of chronic alcohol consumption, can be ameliorated by administration of taurine to rats.     

Amplifying effect of dietary taurine on the induction of cytochrome P-450 and on the urinary excretion of ascorbic acid in rats fed on phenobarbital-containing diets

Dietary taurine amplified the induction of cytochrome P-450 and the urinary excretion of ascorbic acid in rats fed on phenobarbital (PB)-containing diets. These facts suggest that taurine could influence the hepatic metabolism of xenobiotics via the induction of drug-metabolizing enzymes (DME) and the ascorbic acid metabolism. Taurine might improve the function of DME exposed by some xenobiotics.     

Taurine release modified by GABAergic agents in hippocampal slices from adult and developing mice

Summary. In order to characterize the possible regulation of taurine release by GABAergic terminals, the effects of several agonists and antagonists of GABA receptors on the basal and K⁺-stimulated release of [³H]taurine were investigated in hippocampal slices from adult (3-month-old) and developing (7-day-old) mice using a superfusion system. Taurine release was concentration-dependently potentiated by GABA, which effect was reduced by phaclofen, saclofen and (1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid (TPMPA) at both ages, suggesting regulation by both GABA_B and GABA_C receptors. The involvement of GABA_A receptors could not be excluded since the antagonist bicuculline was able to affect both basal and K⁺-evoked taurine release. Furthermore, several GABA_B receptor effectors were able to inhibit K⁺-stimulated taurine release in the adults, while the GABA_C receptor agonists trans-4-aminocrotonic acid (TACA) and cis-4-aminocrotonic acid (CACA) potentiated this release. The potentiation of taurine release by agents acting on the three types of GABA receptors in both adult and developing hippocampus further indicates the involvement of transporters operating in an outward direction. This inference is corroborated by the moderate but significant inhibition of taurine uptake by the same compounds. Received June 28, 1999, Accepted August 31, 1999     

Stabilization of calcium uptake in rat rod outer segments by taurine and ATP

Summary. Calcium ion (Ca²⁺) uptake was measured in rod outer segments (ROS) isolated from rat retina in the presence of varying concentrations of CaCl₂ in the incubation buffer (1.0–2.5 mM). It is known that taurine increases Ca²⁺ uptake in rat ROS in the presence of ATP and at low concentrations of CaCl₂ (Lombardini, 1985a); taurine produces no significant effects when CaCl₂ concentrations are increased to 1.0 and 2.5 mM. With the removal of both taurine and ATP, Ca²⁺ uptake in rat ROS increased significantly in the presence of 2.5 mM CaCl₂. Taurine treatment in the absence of ATP was effective in decreasing Ca²⁺ uptake at the higher levels of CaCl₂ (2.0 and 2.5 mM). Similar effects were observed with ATP treatment. The data suggest that taurine and ATP, alone or in combination, limit the capacity of the rat ROS to take up Ca²⁺ to the extent that a stable uptake level is achieved under conditions of increasing extracellular Ca²⁺, indicating a protective role for both agents against calcium toxicity. Received January 25, 2000/Accepted January 31, 2000     

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