Abstract: Taurine regulates an unusual number of biological phenomena, including heart rhythm, contractile function, blood pressure, platelet aggregation, neuronal excitability, body temperature, learning, motor behavior, food consumption, eye sight, sperm motility, cell proliferation and viability, energy metabolism and bile acid synthesis. Many of these actions are associated with alterations in either ion transport or protein phosphorylation. Although the effects on ion transport have been attributed to changes in membrane structure, they could be equally affected by a change in the activity of the affected transporters. Three common ways of altering transporter activity is enhanced expression, changes in the phosphorylation status of the protein and cytoskeletal changes. Interestingly, all three events are altered by osmotic stress. Since taurine is a key organic osmolyte in most cells, the possibility that the effects of taurine on ion transport could be related to its osmoregulatory activity was considered. This was accomplished by comparing the effects of taurine, cell swelling and cell shrinkage on the activities of key ion channels and ion transporters. The review also compares the phosphorylation cascades initiated by osmotic stress with some of the phosphorylation events triggered by taurine depletion or treatment. The data reveal that certain actions of taurine are probably caused by the activation of osmotic-linked signaling pathways. Nonetheless, some of the actions of taurine are unique and appear to be correlated with its membrane modulating and phosphorylation regulating activities.

Abstract: Using intracerebral microdialysis in urethane-anaesthetized adult male Wistar rats, we monitored the effects of acute repetitive transcranial magnetic stimulation (rTMS; 20 trains of 20 Hz, 2.5 s) on the intrahypothalamic release of arginine vasopressin (AVP) and selected amino acids (glutamate, glutamine, aspartate, serine, arginine, taurine, gamma-aminobutyric acid) and the intrahippocampal release of monoamines (dopamine, noradrenaline, serotonin) and their metabolites (homovanillic acid, 3,4-dihydroxyphenylacetic acid, 5-hydroxyindoleacetic acid). The stimulation parameters were adjusted according to the results of accurate computer reconstructions of the current density distributions induced by rTMS in the rat and human brains, ensuring similar stimulation patterns in both cases. There was a continuous reduction in AVP release of up to 50% within the hypothalamic paraventricular nucleus in response to rTMS. In contrast, the release of taurine, aspartate and serine was selectively stimulated within this nucleus by rTMS. Furthermore, in the dorsal hippocampus the extracellular concentration of dopamine was elevated in response to rTMS. Taken together, these data provide the first in vivo evidence that acute rTMS of frontal brain regions has a differentiated modulatory effect on selected neurotransmitter/neuromodulator systems in distinct brain areas.

Abstract: Background Previous short observational studies on the free amino acid (FAA) content of human milk have shown that glutamine and glutamic acid increase in the first 4 to 6 weeks of life. Methods Changes in human milk content of free amino acids (FAAs) was determined at colostrum, 1 month, and 3 months of lactation in 16 healthy lactating women after delivery of full-term infants. Milk was collected at the end of each feeding (hindmilk) during 24 hours. Results Glutamic acid and taurine were the most abundant FAAs at colostrum. Although taurine remained stable throughout lactation, glutamic acid (the prevalent FAA) and glutamine increased approximately 2.5 and 20 times, respectively, with progressing lactation representing more than 50% of total FAA at 3 months. The content of essential FAA was also stable, so the change in total FAA content was almost entirely due to the changes in glutamic acid and glutamine. Conclusions Breast-fed infants are supplied with progressively increasing amounts of glutamine and glutamic acid throughout lactation. The increasing intake of glutamic acid and glutamine could benefit breast-fed infants with molecules that are likely to protect the enteral mucosa and act as neurotransmitters and as a source of nitrogen.

Abstract: At high osmotic pressures, mammalian kidney medulla, heart, lens, and brain utilize organic osmolytes to regulate cell volume. However the types and proportions of these solutes vary among tissues in patterns and for non-osmotic roles not fully elucidated. To clarify these, we analyzed osmolyte-type solute contents in rat tissues at 7 and 2 days prenatal and at 0, 7, 14, 21 (weaning), 35 (juvenile) and 77 (adult) days postnatal. Placentas were dominated by betaine, taurine, and creatine, which decreased between the prenatal times. Fetuses were dominated by glutamate and taurine, which increased between the times. In cerebrum, hindbrain and diencephalon, taurine dominated at early stages, but dropped after postnatal day 7, while myo-inositol, glutamine, creatine and glutamate increased after birth, with the latter two dominating in adults. In olfactory bulb, taurine content declined gradually with age and was equal to glutamate in adults. In all brain regions, glycerophosphorylcholine (GPC) reached a peak in juveniles. In postnatal renal medulla, urea, sodium, GPC, betaine, and taurine increased sharply at day 21. Thereafter, most increased, but taurine decreased. In heart, taurine dominated, and increased with age along with creatine and glutamine, while glutamate decreased after postnatal day 7. In lens, taurine dominated and declined in adults. These patterns are discussed in light of hypotheses on non-osmotic and pathological roles of these solutes.

Abstract: 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.

Abstract: Selectively bred high-alcohol sensitive (HAS) and low-alcohol sensitive (LAS) rats possess a number of behavioural and electrophysiological differences in their responses to alcohol. Using a microdialysis technique, we have evaluated whether the levels of the amino acids aspartate, glutamate, arginine, taurine, and alanine in HAS and LAS rats differ in their response to ethanol administration (2 g/kg, i.p.). The basal concentrations of each amino acid in these two groups were statistically similar. Following ethanol injection, alanine, arginine, and glutamate were significantly decreased in HAS rats, whereas, alanine, glutamate, and taurine were significantly increased in LAS rats by the end of the experiment. Interestingly, an increase in the sulphonated amino acid taurine was only evident 20 min after ethanol administration in the HAS rats, when compared to saline controls. No changes were observed in the other amino acids studied, aspartate and glycine, after ethanol administration. These data suggest that, in addition to differential behavioural responses to alcohol, HAS and LAS rats also differ in their neurochemical responses to ethanol.

Abstract: 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 1 ] i and Na 1 /Ca 21 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 Ca 21 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.

Abstract: The effects of bile acids on intracellular Ca2+ concentration [Ca2+]i and nitric oxide production were investigated in vascular endothelial cells. Whole-cell patch clamp techniques and fluorescence measurements of [Ca2+]i were applied in vascular endothelial cells obtained from human umbilical and calf aortic endothelial cells. Nitric oxide released was determined by measuring the concentration of NO2−. Deoxycholic acid, chenodeoxycholic acid and the taurine conjugates increased [Ca2+]i concentration-dependently, while cholic acid showed no significant effect. These effects resulted from the first mobilization of Ca2+ from an inositol 1,4,5-triphosphate (IP3)-sensitive store, which was released by ATP, then followed by Ca2+ influx. Both bile acids and ATP induced the activation of Ca2+-dependent K+ current. Oscillations of [Ca2+]i were occasionally monitored with the Ca2+-dependent K+ current in voltage-clamped cells and Ca2+ measurements of single cells. The intracellular perfusion of heparin completely abolished the ATP effect, but failed to inhibit the bile acid effect. Deoxycholic acid and chenodeoxycholic acid enhanced NO2− production concentration-dependently, while cholic acid did not enhance it. The bile acids-induced nitric oxide production was suppressed by NG-nitro-L-arginine methyl ester, exclusion of extracellular Ca2+ or N-(6-aminohexyl)-5-chloro-l-naphthalenesulphonamide hydrochloride (W-7) and calmidazolium, calmodulin inhibitors. These results provide novel evidence showing that bile acids increase [Ca2+]i and subsequently nitric oxide production in vascular endothelial cells. The nitric oxide production induced by bile acids may be involved in the pathogenesis of circulatory abnormalities in liver diseases including cirrhosis. Keywords: Bile acids, vascular endothelial cells, intracellular calcium, nitric oxide, whole-cell clamp techniques Introduction Cirrhosis is associated with marked abnormalities in the systemic circulation. The most common haemodynamic changes in patients with cirrhosis are an increase in cardiac output, a decrease in total systemic vascular resistance and a decrease in arterial pressure (Bosch et al., 1988; Schrier et al., 1988; Groszmann, 1994; Bernardi et al., 1995; Bernardi & Trevisani, 1997; Moller et al., 1997). A reduced presser effect of vasoconstrictor substrates is also a well-documented phenomenon in both humans and animals with cirrhosis (MacGilchrist et al., 1991; Hartleb et al., 1994). Aortic rings from rats with cirrhosis contracted less response to angiotensin II or phenylephrine than aortic rings from normal rats (Castro et al., 1993; Weigert et al., 1995). The basic mechanisms have not yet been clearly elucidated, but, recently, studies in animals and humans have provided evidence suggesting that nitric oxide has an important role in the haemodynamic abnormalities that characterize cirrhosis (Vallance & Moncada, 1991; Niederberger et al., 1995a,1995b; Ros et al., 1995;Martin et al., 1998). Patients with cirrhosis have higher plasma and exhaled air concentration of nitric oxide than normal subjects (Guarner et al., 1993; Matsumoto et al., 1995; Sogni et al., 1995; Battista et al., 1997). The inhibition of nitric oxide synthase such as NG-nitro-L-arginine methyl ester not only restores vascular nitric oxide production but also systemic haemodynamics to normal (Pizcueta et al., 1992; Claria et al., 1992; Weigert et al., 1995; Niederberger et al., 1995a,1995b). The vascular response to vasoconstrictors is also restored by endothelial denudation (Weigert et al., 1995). Thus, these observations implicated increased nitric oxide synthesis of endothelial origin in the haemodynamic changes of cirrhosis. However, the initial cause of overproduction of nitric oxide in vascular endothelial cells has not yet been known. Bile acids are actively secreted and extracted by the liver. Plasma concentrations of bile acids are usually elevated in patients with cirrhosis (Carey, 1958; Makino et al., 1969; 1975; LaRusso et al., 1975; Clain et al., 1977; Pennington et al., 1977), and they have physiological vasoactive properties. Studies on animals show that obstructive jaundice or isolated cholaemia produced by choleductocaval anastomoses induces arterial hypotension due to peripheral vasodilation (Alon et al., 1982; Bomzon et al., 1984; Pak & Lee, 1993), and blunted peripheral presser responses to contractile substrates (noradrenaline and angiotensin) (Finberg et al., 1981; 1982), which are quite similar to haemodynamic changes observed in cirrhosis. Thus, it is most likely that bile acids are implicated as responsible for the haemodynamic changes in cirrhosis, and may act on vascular endothelial cells, then enhancing nitric oxide production. However, until now, the effects of bile acids on vascular endothelial cells have not been investigated. Therefore, the purpose of the present study was to clarify the effects of bile acids on intracellular Ca2+ concentration and nitric oxide production in vascular endothelial cells. Here, we have provided novel evidence showing that bile acids increase [Ca2+]i and then enhance nitric oxide production in vascular endothelial cells.

Abstract: Cell shrinkage is a distinctive feature of apoptotic death, but the mechanisms leading to cell volume loss are unclear at present. Activation of pathways extruding intracellular osmolytes such as K+, Cl– and organic molecules may be part of these mechanisms. This was examined in the present work measuring the release of taurine, γ-amino-butyric acid (GABA) and glutamate in cerebellar granule neurons cultured in conditions resulting in apoptotic death after 4–7 days in vitro (DIV). The basal release of [3H]taurine from cells started to increase (38%) after 3 DIV and reached a maximal enhancement (250%) at 5 DIV. The increase in taurine efflux closely followed the occurrence of apoptotic death markers such as caspase induction and chromatin condensation. The efflux of glutamate (traced as d-aspartate) and [3H]GABA also increased but notably less than that of taurine (90% and 75%, respectively) at 5 DIV. Taurine release associated with apoptosis was unaffected by 4,4'-diisothiocyanatostilbene 2,2'-disulphonic acid (DIDS) and 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB), blockers of the diffusive pathway activated during cell volume regulation in hyposmotic conditions. Taurine efflux was increased in Cl–-free (replaced by gluconate) and decreased in Na+-free media. Blockers of the energy-dependent glutamate and taurine carriers, dihydrokainate and guanidinoethane sulfonate, respectively, did not affect the release associated with apoptosis. These results implicate taurine in the mechanism of cell shrinkage during apoptosis.

Abstract: To characterize the volume-sensitive, osmolyte permeable anion channels responsible for the osmodependent release of taurine from supraoptic nucleus (SON) astrocytes, we investigated the pharmacological properties of the [(3)H]-taurine efflux from acutely isolated SON. Taurine release induced by hypotonic stimulus (250 mosmol l(-1)) was not antagonized by the taurine transporter blocker guanidinoethyl sulphonate, confirming the lack of implication of the transporter. The osmodependent release of taurine was blocked by a variety of Cl(-) channel inhibitors with the order of potency: NPPB>niflumic acid>DPC>DIDS>ATP. On the other hand, release of taurine was only weakly affected by other compounds (dideoxyforskolin, 4-bromophenacyl bromide, mibefradil) known to block volume-activated anion channels in other cell preparations, and was completely insensitive to tamoxifen, a broad inhibitor of these channels. Although the molecular identity of volume-sensitive anion channels is not firmly established, a few genes have been postulated as potential candidates to encode such channels. We checked the expression in the SON of three of them, ClC(3), phospholemman and VDAC(1), and found that the transcripts of these genes are found in SON neurons, but not in astrocytes. Similar observation was previously reported for ClC(2). In conclusion, the osmodependent taurine permeable channels of SON astrocytes display a particular pharmacological profile, suggesting the expression of a particular type or subtype of volume-sensitive anion channel, which is likely to be formed by yet unidentified proteins.

Abstract: The majority of symptomatic patients with congestive heart failure have been shown to be significantly malnourished. Myocardial and skeletal muscle energy reserves are also diminished. Total daily energy expenditure in these patients is less than that in control individuals, and high protein-calorie feeds do not reverse the abnormalities; thus, the wasting that occurs in patients with congestive heart failure is metabolic rather than because of negative protein-calorie balance. Several specific deficiencies have been found in the failing myocardium: a reduction in the content of L-carnitine, coenzyme Q10, creatine and thiamine, nutrient cofactors that are important for myocardial energy production; a relative deficiency of taurine, an amino acid that is integral to the modulation of intracellular calcium levels; and an increase in myocardial oxidative stress, and a reduction of both endogenous and exogenous antioxidant defences. In addition, these processes may influence skeletal muscle metabolism and function. Cellular nutritional requirements conditioned by metabolic abnormalities in heart failure are important considerations in the pathogenesis of the skeletal and cardiac muscle dysfunction. A comprehensive restoration of adequate myocyte nutrition would seem to be essential to any therapeutic strategy designed to benefit patients suffering from this disease.

Abstract: In the supraoptic nucleus, taurine, selectively released in an osmodependent manner by glial cells through volume-sensitive anion channels, is likely to inhibit neuronal activity as part of the osmoregulation of vasopressin release. We investigated the involvement of various kinases in the activation of taurine efflux by measuring [3H]taurine release from rat acutely isolated supraoptic nuclei. The protein tyrosine kinase inhibitors genistein and tyrphostin B44 specifically reduced, but did not suppress, both the basal release of taurine and that evoked by a hypotonic stimulus. Inhibition of tyrosine phosphatase by orthovanadate had the opposite effect. The tyrosine kinase and phosphatase inhibitors shifted the relationship between taurine release and medium osmolarity in opposite directions, suggesting that tyrosine phosphorylation modulates the osmosensitivity of taurine release, but is not necessary for its activation. Genistein also increased the amplitude of the decay of the release observed during prolonged hypotonic stimulation. Potentiation of taurine release by tyrosine kinases could serve to maintain a high level of taurine release in spite of cell volume regulation. Taurine release was unaffected by inhibitors and/or activators of PKA, PKC, MEK and Rho kinase. Our results demonstrate a unique regulation by protein tyrosine kinase of the osmosensitivity of taurine efflux in supraoptic astrocytes. This points to the presence of specific volume-dependent anion channels in these cells, or to a specific activation mechanism or regulatory properties. This may relate to the particular role of the osmodependent release of taurine in this structure in the osmoregulation of neuronal activity. Taurine is an abundant sulfonic β-amino acid present intracellularly at high concentration and best known for its active participation in cell volume regulation (Huxtable, 1992; Pasantes-Morales & Schousboe, 1997). Cells exposed to hypotonic medium swell by water incorporation and progressively recover their initial volume despite the lower tonicity of the extracellular medium through a process known as regulatory volume decrease (RVD; Hoffman & Dunham, 1995; Lang et al. 1998). RVD is achieved via the efflux of inorganic ions and organic osmolytes that include taurine. A large body of evidence supports the notion that taurine leaves the cell upon swelling through ubiquitous, broadly permeable volume-sensitive anion channels, referred to as volume-sensitive organic osmolyte and anion channels (VSOACs), volume-regulated anion channels, or outwardly rectifying Cl− channels (Strange et al. 1996; Okada, 1997; Nilius et al. 1997; Kirk, 1997). This conclusion is based on the one hand on the strong similarities between volume-dependent taurine efflux and swelling-induced Cl− currents through VSOACs with regard to their pharmacological properties, their kinetics of activation, and their implication in volume regulation, and on the other hand on the direct taurine permeability of VSOACs (Strange et al. 1996; Basavappa & Ellory, 1996; Pasantes-Morales & Schousboe, 1997; Kirk, 1997; Nilius et al. 1997; Manolopoulos et al. 1997). However, as mentioned by Kirk (1997), the correspondence between swelling-induced taurine efflux and VSOACs is only correlative, and has yet to be proven, and evidence for alternative taurine pathways has been provided in some cell preparations. VSOACs have been studied in a wide variety of cell preparations, and if these studies agree on several common features of the channels, they also point to different properties depending on the cell model used, notably regarding their activation and regulation. VSOACs are characterised by an outward rectification, an inactivation at positive potentials, a 20–90 pS conductance, a weak selectivity among anions and a high permeability to the organic osmolytes myo-inositol and taurine (Strange et al. 1996; Nilius et al. 1997; Kirk, 1997). The mechanism of activation of VSOACs/taurine efflux upon cell swelling is still poorly understood. It has been argued that membrane stretch is unlikely to directly activate VSOACs (Strange et al. 1996; Okada, 1997; Nilius et al. 1997). Reduction of intracellular ionic strength has been proposed as the initial trigger of channel activation (Voets et al. 1999), although other authors have found that ionic strength regulates the volume sensitivity of the channels (Cannon et al. 1998). In most preparations, activation of VSOACs is independent of changes in intracellular Ca2+ (Strange et al. 1996; Pasantes-Morales & Schousboe, 1997; Okada, 1997). Implication of phosphorylation events is also controversial. Indeed, if VSOAC activation generally requires the presence of intracellular ATP (Strange et al. 1996; Basavappa & Ellory, 1996; Nilius et al. 1997; Crepel et al. 1998; Miley et al. 1999), its hydrolysis is not necessary in many cell preparations as ATP can be replaced by non-hydrolysable analogues (Strange et al. 1996; Okada, 1997; Nilius et al. 1997; Miley et al. 1999; Bond et al. 1999). This observation argues for a lack of involvement of protein kinases in the activation mechanism. On the other hand, ATP hydrolysis appears critical in other cell preparations (Meyer & Korbmacher, 1996; Crepel et al. 1998), and protein tyrosine kinases (PTKs) have been proposed to play a pivotal role in the activation of VSOACs in many cell types including cultured astrocytes (Crepel et al. 1998; Mongin et al. 1999), cardiac myocytes (Sorota, 1995), lymphocytes (Lepple-Wienhues et al. 1998), endothelial (Voets et al. 1998) and epithelial cells (Tilly et al. 1993). In cultured astrocytes, this process requires further activation of the mitogen-activated protein kinases (MAPK) Erk1 and Erk2 (Crepel et al. 1998). However, an inhibitory effect of increased tyrosine phosphorylation has also been reported (Doroshenko, 1998; Thoroed et al. 1999). Conflicting results also exist as to the role of protein kinase A (PKA), protein kinase C (PKC), or calmodulin kinase II depending on the cell preparation (Basavappa & Ellory, 1996; Strange et al. 1996; Kirk, 1997; Nilius et al. 1997; Okada, 1997). In several cell types, volume-sensitive Cl− currents can also be triggered by GTP-binding protein activation (Doroshenko et al. 1991; Nilius et al. 1997, 1999). Moreover, inhibition of either Rho protein (Tilly et al. 1996; Nilius et al. 1999) or Rho kinase (Nilius et al. 1999) affects activation of VSOACs, suggesting the involvement of small GTP-binding proteins of the Rho family in the regulation or the activation of the channel. In the hypothalamic supraoptic nucleus (SON), taurine, which is prominently concentrated in glial cells (Decavel & Hatton, 1995), is released through volume-activated Cl− channels in response to hypotonic swelling (Deleuze et al. 1998). Release of taurine is highly sensitive to even minute, physiological changes in extracellular osmotic pressure (Deleuze et al. 1998). Such small stimuli apparently do not induce RVD, since the resulting release of taurine is sustained as long as the stimulus is applied (Deleuze et al. 1998). Rather, release of glial taurine induced by these weak decreases in osmolarity would contribute to the control of the electrical activity of SON neurones as part of the osmoregulation of vasopressin secretion (Hussy et al. 1997). As an effort to characterise the mechanism of activation of the volume-dependent channel carrying taurine efflux in SON, we studied the influence of tyrosine phosphorylation on the activation and osmosensitivity of taurine release from acutely isolated SON. Our results point to an important regulatory role of tyrosine phosphorylation on the osmosensitivity of volume-activated taurine-permeable Cl− channels, but with no direct implication in the cascade of events leading to activation of the efflux pathway. A preliminary account of these results has appeared in abstract form (Deleuze et al. 1999).

Abstract: During ethanol withdrawal, dramatic changes in the concentration of many neurotransmitters may be responsible for many of the adverse effects. In the present study, the technique of microdialysis was used to assay the changes in excitatory and inhibitory amino acids after withdrawal from chronic ethanol intoxication. Rats were made physically dependent on ethanol by vapor inhalation for 4 weeks. The basal concentrations of both arginine and GABA were significantly decreased in ethanol-dependent rats, although there were no significant changes in any of the other amino acid basal concentration assayed (i.e.. glutamate and taurine). During the first 12 h after withdrawal from ethanol, only glutamate increased significantly (p < 0.05) at 6 h, and for the duration of the study period of 12 h. To investigate whether either taurine and ethanol interact with amino acids during ethanol withdrawal, two other ethanol-dependent groups were injected with a single intraperitoneal injection of either taurine or ethanol 5 h after commencement of ethanol withdrawal. The IP injection of ethanol (2 g/kg) significantly increased taurine microdialysate content, and although this dose of ethanol was not able to block completely the increase of glutamate release after ethanol withdrawal, a delayed decrease in glutamate content was observed by the end of the period of the study (i.e., 11-12 h). However, IP injection of taurine (45 mg/kg) significantly blocked the increased glutamate release during ethanol withdrawal. This latter finding suggests that taurine may interact with glutamate, possibly by inducing a blockade of glutamate release during ethanol withdrawal.

Abstract: The amino acid taurine has been implicated in several aspects of reproductive system physiology. However, its localization in these organs has not been previously analyzed. The aim of this study was to characterize its distribution in male rat reproductive organs by immunohistochemical methods. Taurine was localized in the smooth muscle cells of the tissues studied and in the skeletal fibers of the cremaster muscle. In the testis, taurine was found in Leydig cells, vascular endothelial cells, and other interstitial cells. No immunoreactivity was observed in the cells of the seminiferous tubules, either in germ cells at all spermatogenic stages or in Sertoli cells. However, peritubular myoid cells were immunostained. Most epithelial cells of the efferent ducts were immunolabeled, whereas the epithelial cells of the rete testis (extratesticular segments), epididymis (caput, corpus, and cauda regions), and ductus deferens were unstained. However, most epithelial cells from the intratesticular segments of the...

Abstract: Following a delay of 45 min, stimulation of the CD95 (Fas/Apo-1)-receptor in Jurkat T-lymphocytes leads to the release of the osmolyte taurine, an event coinciding with apoptotic cell shrinkage The present study has been performed to elucidate the cellular mechanisms involved in CD95-induced taurine release as compared to swelling-induced taurine release, and to explore whether taurine modifies apoptotic DNA fragmentation and cell shrinkage Taurine release stimulated by osmotic cell swelling is insensitive to the tyrosine kinase inhibitor herbimycin A and the caspase inhibitor z-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD) but is blunted in the absence of extracellular Ca2+ Conversely, the Ca2+ ionophore ionomycin stimulates taurine release However, the taurine release following CD95 stimulation is not paralleled by an increase of cytosolic Ca2+ and not inhibited by complexation of extracellular Ca2+ None of herbimycin A, the phosphatase inhibitor vanadate, spingomyelinase or Lck56 deficiency prevent CD95-induced taurine release In contrast, the caspase inhibitor zVAD, but not the caspase inhibitor Ac-Tyr-Val-Ala-Asp-chloromethylketone (YVAD), almost abolishes CD95-induced taurine release Both caspase inhibitors blunt CD95-induced cell shrinkage and DNA fragmentation, zVAD being more effective than YVAD Preloading of the cells with 40 mM taurine but not with 40 mM mannitol significantly inhibits CD95-induced DNA fragmentation (by 28%) and apoptotic cell shrinkage (by 25%) In conclusion, CD95-receptor triggering leads to caspase-dependent stimulation of cellular taurine release, which facilitates, but is not sufficient for, the triggering of apoptotic DNA fragmentation and cell shrinkage

Abstract: The role for nerve blood flow (NBF) vs. other factors in motor nerve conduction (MNC) slowing in short-term diabetes was assessed by evaluating α1-adrenoceptor antagonist prazosin on NBF, MNC, as well as metabolic imbalances and oxidative stress in the neural tissue. Control and diabetic rats were treated with or without prazosin (5 mg·kg−1·d−1 for 3 wk). NBF was measured by hydrogen clearance. Both endoneurial vascular conductance and MNC velocity were decreased in diabetic rats vs. controls, and this decrease was prevented by prazosin. Free NAD+:NADH ratios in mitochondrial cristae, matrix, and cytosol assessed by metabolite indicator method, as well as phosphocreatine levels and phosphocreatine/creatine ratios, were decreased in diabetic rats, and this reduction was ameliorated by prazosin. Neither diabetes-induced accumulation of two major glycation agents, glucose and fructose, as well as sorbitol and total malondialdehyde plus 4-hydroxyalkenals nor depletion of myo-inositol, GSH, and taurine or decr...

Abstract: A natural polysaccharide, chitosan (poly-N-acetyl glucosaminoglycan), which is a nontoxic and bioabsorbable polymer, has been shown to have hemostatic and antibacterial effects. An amino acid, taurine, is considered to be beneficial for regulating the inflammation process. The purpose of this study was to investigate the synergistic effects of taurine and chitosan in the experimental defects at the vestibular bone of maxillary canine teeth in six dogs. Chitosan films were prepared as delivery system with or without taurine and placed in the randomly chosen defects. Biopsies were performed on the postoperative seventh day and routine histological procedures were performed for light and electron microscopic evaluations. For each group, 30 different microscopic areas were examined and the numbers of macrophages and neutrophils in these areas were counted. The mean numbers of both macrophages and neutrophils were found statistically different between the chitosan film incorporated with taurine and free chitosan groups (p 0.05). In addition to the increase in cell counts in both groups, the cytological alterations were more obvious in the chitosan film group incorporated with taurine. Accordingly, taurine appears to enhance the acceleration effect of chitosan on wound healing at early periods. This effect could be considered beneficial in tissue repair in destructive diseases like periodontitis.