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Amino Acids: The Forum for Amino Acid, Peptide and Protein Research (v.15, #1-2)
Changes in mediobasal hypothalamic dopamine and GABA release: A possible mechanism underlying taurine-induced prolactin secretion by Prof. Dr. Pablo Arias; H. Jarry; V. Convertini; M. Ginzburg; W. Wuttke; J. Moguilevsky (pp. 5-11).
Taurine (Tau), a putative inhibitory amino acid neurotransmitter, has been shown to stimulate prolactin (PRL) release. Using ovariectomized, estrogen-replaced adult rats we investigated initially the effect of this amino acid, injected by different routes, on PRL secretion in vivo. Tau (100–500 mg/kg) had no effect on PRL release when given i.p.; 15 min after i.c.v. injection of Tau (3μmoles), a significant increase in serum PRL levels was observed (78 ± 9 ng/ml over basal levels, p < 0.01 vs. controls). In vitro (cultured anterior pituitary cells) PRL release was not affected by a 5 h incubation with Tau (10−3–10−8 M). Basal dopamine (DA) or gamma-aminobutyric acid (GABA) output from superfused mediobasal hypothalamic fragments (MBH) was not affected by Tau (10−3 M or 10−5 M). However, during stimulation with KCl (50mM), Tau (10−3 M) significantly lowered DA release, and increased GABA output. It is concluded that Tau acts at a central level to increase PRL secretion, most probably by modulating the hypothalamic release of neurotransmitters controlling lactotroph function.
Keywords: Amino acids; Taurine; Prolactin; Dopamine; GABA; HPLC; Hypothalamus
The effects of theβ2-agonist drug clenbuterol on taurine levels in heart and other tissues in the rat by M. H. Doheny; C. J. Waterfield; Prof. John A. Timbrell (pp. 13-25).
The administration of a single subcutaneous dose of clenbuterol to rats altered the level of taurine in certain tissues. Taurine levels in cardiac tissue were significantly decreased 3 h after the administration of 250μg/kg of clenbuterol and remained significantly depressed at 12h post-dose only returning to control values by 24h. The level of taurine in the liver increased 3 h after clenbuterol administration but was lower than the control value at 24 h post dose. Lung taurine levels were significantly lower than the control value at 12 hr post dose and remained depressed until 24h post dose. Clenbuterol caused a significant increase in taurine levels in serum and muscle at 3 and 6 hr postdosing respectively but not at other time points. Serum creatine kinase (CK), activity was slightly but significantly raised at the 12 and 24 h time point.The effects of clenbuterol on tissue taurine content were not dose-dependent over the range studied (63–500μg/kg). However taurine levels in the lung were significantly reduced at all doses and in the heart were significantly lower in the treated groups at all except the lowest dose, 12h post dosing. Liver taurine levels were significantly increased at the highest dose of 500μg/kg.The reduction of taurine concentrations in the heart, caused by clenbuterol, is of concern as taurine has been shown to have protective properties in many tissues especially the heart.
Keywords: Amino acids; β-Adrenoceptor agonist; Clenbuterol; Taurine
Precursors of taurine in female genital tract: Effects on developmental capacity of bovine embryo producedin vitro by Catherine Guyader-Joly; P. Guérin; J. P. Renard; J. Guillaud; S. Ponchon; Y. Ménézo (pp. 27-42).
Two precursors of taurine have been studied: cysteamine and hypotaurine. Cysteamine has been quantified in genital secretions and found in follicular fluids of all species tested. On the contrary cysteamine was not detected (or traces) in tubal fluids of the same species. Addition of 50, 100 or 250μM of cysteamine to the maturation medium used in the culturing of bovine oocytes did not improve the cleavage rate nor the embryo's developmental potentialin vitro. Furthermore, at 250μM, cysteamine seems to be toxic to the embryo. Addition of 0.5–1 mM hypotaurine to the bovine embryo culture medium improved significantly blastocyst production and quality. The respective roles of these 2 taurine precursors on maturation and embryo development are discussed.
Keywords: Amino acids; Cysteamine; Cystamine; Hypotaurine; Taurine; Bovinein vitro embryo production; Follicular fluid; Oviduct fluid
Activation of adenosine A2 receptors enhances high K+-evoked taurine release from rat hippocampus: A microdialysis study by Dr. Junichi Hada; T. Kaku; K. Morimoto; Y. Hayashi; K. Nagai (pp. 43-52).
The present study was designed to examine which type of adenosine receptors was involved in enhancement of high K+-evoked taurine release fromin vivo rat hippocampus using microdialysis. Perfusion with 0.5 or 5.0 mM adenosine enhanced high K+-evoked taurine release. Perfusion with 2μM R(−)-N6-2-phenylisopropyladenosine (PIA), a selective adenosine A1 receptor agonist, did not modulate taurine release. Perfusion with 1μM 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), a selective adenosine A1 receptor antagonist, increased taurine release. On the other hand, perfusion with 20μM 2-[4-(2-carboxyethyl)phenethylamino]-5′-N-ethyl-carboxamideadenosine (CGS21680), a selective adenosine A2A receptor agonist, enhanced taurine release, while perfusion with 1 mM 3,7-dimethyl-propagylxanthine (DMPX), an adenosine A2 receptor antagonist, did not affect taurine release. These results demonstrate that adenosine enhances high K+-evoked taurine release via activation of adenosine A2A receptors from both neurons and glial cells ofin vivo rat hippocampus.
Keywords: Amino acids; Adenosine; Taurine; Hippocampus; Microdialysis; Spreading depression
Taurine: Protective properties against ethanol-induced hepatic steatosis and lipid peroxidation during chronic ethanol consumption in rats by M. D. J. Kerai; Dr. Catherine J. Waterfield; S. H. Kenyon; D. S. Asker; J. A. Timbrell (pp. 53-76).
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.
Keywords: Amino acids; Taurine; Ethanol; Protection; Hepatic steatosis; Lipid peroxidation; CYP2E1; Homocysteine; Methionine synthase
Effects of taurine depletion on cell migration and NCAM expression in cultures of dissociated mouse cerebellum and N2A cells by T. E. Maar; T. M. Lund; G. Gegelashvili; R. Hartmann-Petersen; J. Moran; H. Pasantes-Morales; V. Berezin; E. Bock; Prof. Arne Schousboe (pp. 77-88).
Cultures of dissociated cerebellum from 5- to 6-day-old mice as well as of the N2A neuronal cell line were exposed to guanidino ethane sulfonate (GES, 2–5 mM) to reduce the cellular taurine content. Control cultures were kept in culture medium or medium containing 2–5 mM GES plus 2–5 mM taurine to restore the intracellular taurine content. Taurine depletion led to changes in the expression of certain splice variants of NCAM mRNA such as the AAG and the VASE containing forms, while no differences were seen in the expression of the three forms of NCAM protein. In the N2A cells taurine depletion led to a decreased migration rate of the cells. The results suggest that the reduced migration rate of neurons caused by taurine depletion may be correlated to changes in expression of certain adhesion molecules such as NCAM. Moreover, taurine appears to be involved in regulation of transcription processes.
Keywords: Amino acids; Taurine; Neurons; NCAM; Migration; Transcription
Antidiuretic hormone infusion reduces taurine and NaCl-induced hypernatremia in the rats by M. J. McBroom Ph. D.; A. Qureshi; N. Davidson (pp. 89-97).
Rats drinking taurine and hypertonic saline (T + S) develop severe hypernatremia, but rats drinking either T or S alone do not. One hypothesis for this disruption of homeostasis is that the T + S combination interferes with the actions of antidiuretic hormone (ADH). Rats drinking T + S developed severe hypernatremia (170 mmol/L) by day 8 when infused with distilled water by osmotic minipumps, but maintained plasma sodium below 150 mmol/ L when infused with ADH. Cumulative water balance in T + S drinkers receiving ADH was consistently higher than in those not receiving ADH. However the ratio of cumulative sodium balance to cumulative water balance suggests little uniform advantage to rats receiving ADH nor does comparison of urine osmolality in the two groups. Precisely how ADH administration reduces hypernatremia in T + S drinking rats remains unclear, but the hypothesis that T + S interferes with the action of ADH in its regulation of extracellular fluid volume and osmolality remains viable.
Keywords: Amino acids; Taurine; Hypernatremia; Antidiuretic hormone; Salt and water balance
Pharmacological characterization of the effects of taurine on calcium uptake in the rat retina by J. D. Militante; J. B. Lombardini Ph. D. (pp. 99-108).
Taurine is known to increase ATP-dependent calcium ion (Ca2+) uptake in retinal membrane preparations and in isolated rod outer segments (ROS) under low calcium conditions (10μM) (Pasantes-Morales and Ordóñez, 1982; Lombardini, 1991). In this report, ATP-dependent Ca2+ uptake in retinal membrane preparations was found to be inhibited by 5μM cadmium (Cd2+), suggesting the involvement of cation channel activation. The activation of cGMP-gated cation channels, which are found in the ROS, is a crucial step in the phototransduction process. An inhibitor of cGMP-gated channels, LY83583, was found to inhibit taurine-stimulated ATP-dependent Ca2+ uptake but had no effect on ATP-dependent Ca2+ uptake in the absence of taurine, indicating that taurine may be increasing ATP-dependent Ca2+ uptake through a mechanism of action involving the opening of cGMP-gated channels. The activation of cGMP-gated channels with dibutyryl-cGMP and with phosphodiesterase inhibition using zaprinast caused an increase in ATP-dependent Ca2+ uptake in isolated ROS, but not in taurine-stimulated ATP-dependent Ca2+ uptake. LY83583 had the same effects in isolated ROS as in retinal membrane preparations. Another inhibitor of cGMP-gated channels, Rp-8-Br-PET-cGMPS, produced the same pattern of inhibition in isolated ROS as LY83583. Thus, there appears to be a causal link between taurine and the activation of the cGMP-gated channels in the ROS under conditions of low calcium concentration, a connection that suggests an important role for taurine in the visual signalling function of the retina.
Keywords: Amino acids; Calcium uptake; Taurine; Rod outer segments; cGMP-gated channels
Renal excretory responses of taurine-depleted rats to hypotonic and hypertonic saline infusion by Dr. M. S. Mozaffari; B. K. Warren; J. Azuma; S. W. Schaffer (pp. 109-116).
Male Wistar-Kyoto rats were given either tap water (control) or 3%β-alanine (taurine-depleted) for three weeks. To prepare for the kidney function studies, the animals were then implanted with femoral vessels and bladder catheters. Two days after surgery, each rat was given an intravenous infusion of saline at the rate of 50μl/min and urine samples were collected at specific time intervals. An isotonic saline solution (0.9% NaCl) was infused for determination of baseline parameters and was followed by the infusion of a hypotonic saline solution (0.45% NaCl). Two days later, the infusion protocol was repeated in the same animals; however, a hypertonic saline solution (1.8% NaCl) was substituted for the hypotonic saline solution. Renal excretion of fluid and sodium increased in the control, but not taurine-depleted, rats during the hypotonic saline infusion. Interestingly, diuretic and natriuretic responses were similar between the groups during hypertonic saline infusion. The results suggest that taurine-depletion in rats affects renal excretory responses to a hypotonic, but not a hypertonic, saline solution.
Keywords: Amino acids; Taurine; Rat; Natriuresis; Hypotonic saline; Hypertonic saline
Locally infused taurine, GABA and homotaurine alter differently the striatal extracellular concentrations of dopamine and its metabolites in rats by Dr. M. Ruotsalainen; M. Majasaari; J. Salimäki; L. Ahtee (pp. 117-134).
We studiedin vivo the effects of locally infused taurine (50, 150, and 450 mM) on the striatal dopamine and its metabolites in comparison with those of GABA and homotaurine, a GABAA receptor agonist, in freely moving rats. The extracellular dopamine concentration was elevated maximally 2.5-, 2- and 4-fold by taurine, GABA and homotaurine, respectively. At 150 mM concentration, at which the maximum effects occurred, homotaurine increased the extracellular dopamine more than taurine or GABA. When taurine and GABA were infused simultaneously with tetrodotoxin the output of dopamine did not differ from that in the presence of tetrodotoxin alone. In comparison, tetrodotoxin did not inhibit the increase in extracellular dopamine caused by homotaurine. Furthermore, omission of calcium from the perfusion fluid inhibited the increase of extracellular dopamine caused by GABA. However, it did not block the increase of dopamine caused by taurine or homotaurine. The present study suggests that the effects of intrastriatal taurine, GABA and homotaurine on the striatal extracellular dopamine differ. Thus, these amino acids seem to affect the striatal dopaminergic neurons via more than one mechanism.
Keywords: Amino acids; Striatal dopamine release; Intrastriatal taurine; GABA; Homotaurine; Microdialysis; Rat
Shape and size changes induced by taurine depletion in neonatal cardiomyocytes by Dr. Stephen V. W. Schaffer; C. Ballard-Croft; J. Azuma; K. Takahashi; D. G. Kakhniashvili; T. E. Jenkins (pp. 135-142).
Taurine is a very important organic osmolyte in most adult cells. Because of this property it has been proposed that large changes in the intracellular content of taurine can osmotically stress the cell, causing changes in its size and shape. This hypothesis was examined by measuring cell dimensions of taurine deficient cardiomyocytes using confocal microscopy. Incubation of isolated neonatal rat myocytes with medium containing 5mMβ-alanine led to a 55% decrease in intracellular taurine content. Associated with the loss of taurine was a reduction in cell size. Two factors contributed to the change in cell size. First, there was a shift in cell shape, favoring the smaller of the two cellular configurations commonly found in the myocyte cell culture. Second, the size of the polyhedral configuration was reduced after ßalanine treatment. These same two events also contributed to size reduction in cardiomyocytes incubated with medium containing 30mM mannitol. Nonetheless, some qualitative differences exist between cells osmotically stressed by increasing the osmolality of the incubation medium and decreasing intracellular osmolality. The results support a role for taurine in the regulation of osmotic balance in the neonatal cardiomyocyte.
Keywords: Amino acids; Taurine; Osmoregulation; Cell size; Cell shape
Expression and localization of cysteine dioxygenase mRNA in the liver, lung, and kidney of the rat by M. Shimadal M. D. Ph. D.; T. Koide; E. Kuroda; N. Tsuboyama; Y. Hosokawa; M. Watanabe (pp. 143-150).
The expressions of cysteine dioxygenase (CDO) gene in the liver, lung, skeletal muscle, and kidney were studied byin situ hybridization with a cDNA probe from rat liver CDO under normal conditions. Significant expression of the CDO gene was detected in the liver, lung, and kidney, but not skeletal muscle. In the liver, the signal was confined to the cytoplasm of the hepatocytes. Furthermore, the signal was stronger in the periportal than that in the perivenous areas. In the lung, an intensive signal was found in the bronchiolar epithelium. As to the kidney, an intensive signal was observed in the distal convoluted tubules, while no signal was found in the proximal convultions.
Keywords: Amino acids; In situ hybridization; Cysteine dioxygenase; Liver; Lung; Kidney; Rat
Immunohistochemical localization of taurine in various tissues of the mouse by Akiko Terauchi; A. Nakazaw; K. Johkura; L. Yan; N. Usuda (pp. 151-160).
The localization of taurine was investigated in several tissues of the mouse. Immunohistochemical methods using a polyclonal antibody for taurine derived from rabbits was used in these studies. This method was used since it is a simple procedure and the results are clear and reliable. Tissues were fixed with paraformaldehyde, embedded in paraffin and treated in a microwave oven before using an avidin-biotin-complex method (ABC method). Control staining was accomplished by employing absorption staining using various amino acids: taurine, arginine, cysteine, hypotaurine and others. For purposes of comparison, radioautography (RAG) with3H-taurine was performed to confirm the reliability of the immunohistochemical staining compared with the localization of the3H-taurine incorporation in endothelial cells of the blood vessels of several tissues. In this investigation, immunoreactivity was broadly observed in many tissues: Purkinje cells of the cerebellum, glia cells of brain tissue, cardiac muscle cells, matrices of the bone, mucus granules of goblet cells of the intestines, and brown adipose cells of the fetus. Although the meaning of this widespread localization of taurine can not be explained completely, we surmise that taurine may have a different function in each of the tissues. In addition, taurine reactivity was observed in cell nuclei which was evidence of the presence of taurine in the nuclei.
Keywords: Amino acids; Taurine; Taurine-antibody; 3H-Taurine
Is there a correlation between taurine levels and xenobioticinduced perturbations in protein synthesis?: A study with tetracycline in rats by Dr. Catherine Waterfield; D. S. Asker; S. Paten; J. A. Timbrell (pp. 161-177).
Changes in urinary levels of taurine have been reported in rats following treatment with various xenobiotics including those which alter protein synthesis and/or are hepatotoxic. This paper reports on the time course of the urinary elevation of taurine following treatment of rats with tetracycline (50, 150 and 200mg.kg-1). Maximum taurine excretion occurred 8–12h following dosing. Serum albumin and total protein were significantly lower after 24h (200mg.kg-1). The increase in urinary taurine was dose-related and reflected in the raised serum levels of taurine 24h after dosing. Serum and urinary protein and [3H]-leucine incorporation into acid precipitable protein in liver and muscle were reduced by tetracycline (100, 150 and 200mg.kg-1) 10h after dosing. The reduction in protein synthesis was correlated with increased urinary and serum levels of taurine at 10h. The use of taurine as a non-invasive marker of protein synthesis is discussed.
Keywords: Amino acids; Taurine; Protein synthesis; Urinary marker; Tetracycline; Glutathione
Effects ofin vivo taurine depletion on induced- chemiluminescence production in macrophages isolated from rat lungs by X. Zhang; J. B. Lombardini Ph.D. (pp. 179-186).
Alveolar macrophages isolated by pulmonary lavage from partially taurine-depleted ratsdemonstrated increased (2–2.6 fold) chemiluminescence due to the extracellular reaction between exogenous zymosan and various reactive forms of oxygen compared to macrophages isolated from control animals. Partial taurine depletion was achieved by adding 3% ß-alanine to the drinking water of the rats for 5 weeks prior to harvesting the macrophages. Superoxide dismutase activity was not increased in the lung tissue of the taurine-depleted rats. These data suggest that taurine has antioxidant properties and that taurine depletion is potentially deleterious to alveolar macrophages and pulmonary tissue.
Keywords: Amino acids; Taurine; Superoxide anion; Chemiluminescence; Superoxide dismutase; Macrophage