Abstract: Taurine is one of those enigmatic substances about which so much, and so little, is known. It is a simple substance, with a molecular weight of 125 and a molecular formula of C2H7O3NS. Taurine occurs in high concentration in many mammalian tissues, comprising in excess of 60% of the total free amino acid pool in the rat heart. Furthermore, it is one of the most abundant amino acids in the brain. Taurine, which was first isolated from bull’s urine in 1827 (Tiedemann and Gmelin, 1827), is a substance of high chemical stability and low metabolic reactivity. In mammals, only one potential pathway for the degradation of taurine has been proposed, that being the conversion to isethionic acid, but the evidence for this pathway is tenuous (Huxtable, 1978). Analysis of taurine can be readily achieved by a number of simple colorimet-ric tests in the laboratory, or it can be detected by an amino acid analyzer, on which it is one of the first substances eluted.

Abstract: we compared amino acid contents of 54 epileptogenic foci removed neurosurgically from temporal or frontal cortex of 35 patients with focal epilepsy with those of biopsies from the same cortical regions of 14 nonepileptic patients. Neither taurine nor GABA content was reduced in epileptogenic foci. Glycine content was elevated markedly in some foci, whereas aspartic acid content was normal. Mean glutamic acid content was significantly higher in epileptogenic foci than in control cortex, and six foci contained amounts of glutamate more than 2 SD above the control mean. Our findings do not support hypotheses that deficiencies of taurine or GARA are involved in the pathogenesis of focal epilepsy but do suggest a possible etiologic role for the excitatory neurotransmitter, glutamic acid.

Abstract: It is well established that taurine plays an important role in the maintenance of intracellular osmolal concentration in marine invertebrates, teleosts, and amphibians. In fresh water, concentrations of taurine in body tissues decrease; in salt water, they increase. In this study with mice we found that during adaptation of these mammals to chronic hypernatremia, the taurine content of the heart increased; concentrations of other amino acids were unchanged or were decreased. Welty and his associated have shown that acute hyponatremia lowered the taurine concentration of rat heart. In concert, these data suggest that taurine also may serve as an osmotic agent in mammalian heart.

Abstract: The effect of prolonged treatment (10 days) with the anticonvulsant drugs diphenylhydantoin (DPH), phenobarbitone, sodium valproate, ethosuximide and sulthiame, both singly and in combination, on regional rat brain amino acid neurotransmitter concentrations (GABA, glutamate, aspartate and taurine) were assessed. DPH had a major effect in the cerebellum and hypothalamus in that it significantly reduced cerebellar GABA. taurine and aspartate and hypothalamic GABA and aspartate. Sodium valproate significantly elevated GABA and taurine in most regions. Aspartate and glutamate were less affected. Phenobarbitone significantly elevated GABA concentrations in all brain regions, while taurine concentration was only elevated in the cerebral cortex. Ethosuximide induced changes were small compared to the other anticonvulsants while sulthiame produced complex changes. Anticonvulsant drugs administered in combination resulted in complex changes, suggesting that their mode of action is different.

Abstract: The purpose of this study was to determine the most critical substrate or metabolic parameters from among a large number of plasma substances which would predict patient survival or demise in the trauma-septic state. Twenty-five septic patients (14 survivors, 11 nonsurvivors) with 102 analyses were evaluated. Levels of amino acids were analyzed on a pattern basis by use of fractional concentrations (Z values), the ratio of the individual amino acid concentration to the total concentration of either the essential or nonessential amino acids according to the amino acid type. Patients who did not survive (in contrast to survivors) had significantly lower Z values for Ser, Glu, Gly, Val, He, Leu, and Arg, and higher Z values for Asp, Thr, Asn, Pro, Ala, Met, Phe, His, and Trp, all of which indicated marked pattern distortions between the two patient sets. Concentrations of plasma substances reduced in patients who did not survive were taurine, alpha- 1-acid glycoprotein, and ceruloplasmin, and increased were alpha-aminobutyrate, urea, glucose, free fatty acids, triglycerides, lactate, retinol-binding protein, cortisol, and glucagon. Using the same patient data base discriminant analyses, a further form of pattern evaluation, were conducted between the patient groups. With these analyses, patients who later succumbed could be identified 9 days before demise with 99% certainty from a single plasma analysis profile. The variables with greatest discriminant power, in decreasing order, were urea, lactate, the sum of the nonessential amino acids (negative), alpha-aminobutyrate, glucagon, glucose, Z glutamine, Z aspartate, Z asparagine, ornithine (negative), AO2, alpha-1-acid glycoprotein, Z valine (negative), ceruloplasmin (negative), alpha-2-HS glycoprotein, pyruvate (negative), and Z phenylalamine. Alterations in metabolism as reflected in plasma substrate patterns are thus critical indicators of a degrading septic state.

Abstract: The K+-stimulated, Ca2+-dependent release of glutamate, aspartate, -γ-aminobutyric acid (GABA), alanine, taurine, and glycine was measured in slices of cerebella obtained from control, and granule cell-, granule cell plus stellate cell-, or climbing fiber-deficient cerebella of the rat. The 55 mm-K+-stimulated release of glutamate and GABA was 10-fold greater in the presence of Ca2+ than in its absence. The stimulated release of aspartate was 4-fold higher when Ca2+ was present in the bathing media, while the value for alanine was twice as high as the amount obtained in the absence of Ca2+. There was no stimulated release of either taurine or glycine from the cerebellar slices. Increasing the Mg2+ concentration to 16 HIM inhibited the K+-stimulated, Ca2+-dependent release of glutamate, GABA, aspartate, and alanine 85% or more. The K+-stimulated, Ca2+ dependent release of glutamate, aspartate, and alanine from x-irradiated cerebella deficient in granule cells was reduced to 50–57% of control value. Additional x-irradiation treatment, which further reduced the cerebellar granule cell population and also prevented the acquisition of stellate cells, decreased the release of glutamate by 77%, aspartate by 66%, alanine by 91%, and, in addition, decreased the release of GABA by 55%. The K+-stimulated, Ca2+-dependent release of glutamate, aspartate, GABA, and alanine was not changed in climbing fiber-deficient cerebella obtained from 3-acetylpyridine-treated rats. The data support a transmitter role for GABA and glutamate in the cerebellum, but do not support a similar function for either taurine or glycine. The data also suggest that alanine and aspartate may be co-released along with glutamate from granule cells.

Abstract: Taurine and hypotaurine were examined for their efficacy in replacing sperm motility factor (SMF), prepared from bovine adrenal cortex, for in vitro fertilization in the golden hamster. Combinations of these amino acids at concentrations of 0.001, 0.01, 0.1, and 1 mM together with 16 μM isoproterenol (a catecholamine β-agonist) were added to the sperm incubations. After three hours of sperm preincubation, oviductal eggs were added to the sperm suspensions and examined for penetration and stage of fertilization after three or five hours of culture. At 0.001 mM, neither taurine or hypotaurine was capable of maintaining motility of hamster sperm for four to 4½ hours or of inducing fertilization. With all other concentrations, both amino acids were found to maintain motility of sperm as well as SMF. Hypotaurine stimulated motility to a greater extent than taurine and both required isoproterenol for the greatest motility. A low proportion of cumulus-free ova were fertilized when sperm were preincubated with either amino acid alone over the range of 0.01 to 1 mM; however, over 80% fertilization was consistently obtained when isoproterenol was also present during sperm incubation. Proportions of ova fertilized with taurine or hypotaurine present during sperm preincubation were comparable to those achieved with SMF. The possibility that taurine or hypotaurine is the sperm motility factor is discussed. After three hours of sperm/egg incubation, a lag in the early events of fertilization was observed in experimental groups treated with one of the amino acids (0.01 mM) alone compared with groups treated with isoproterenol present. However, if sperm/egg incubation was extended from three to five hours, no increase in number of eggs penetrated was found. Therefore, the delay observed at three hours was considered a function of fewer numbers of capacitated sperm present in the absence of isoproterenol rather than of the need for an extended capacitation time.

Abstract: The central cardiovascular effects of taurine were compared with those of homotaurine and muscimol. The drugs were injected i.c.v. in cumulative doses into pentobarbital-anesthetized cats. Muscimol (0.1-30 microgram/kg) produced dose-dependent hypotension and bradycardia, with a maximum effect of 70 +/- 5 mm Hg and 75 +/- 5 beats/min, respectively. Homotaurine led to a dose-related fall in blood pressure and heart rate; maximum effects were obtained with 300 microgram/kg and averaged 55 +/- 3 mm Hg and 73 +/- 3 beats/min. For both drugs, the dose-response curves were shifted to the right by pretreatment with 10 microgram/kg of bicuculline i.c.v. This antagonism confirms that the central cardiovascular effects of muscimol and homotaurine are mediated by a stimulation of gamma-aminobutyric acid receptors. Taurine produced dose-related hypotension and bradycardia. The depressive effects of taurine started at a dose of 10 microgram/kg; at a dose of 1000 microgram/kg, the maximum effects observed were a 55 +/- 7 mm Hg hypotension and a 53 +/- 8 beats/min bradycardia. These effects were not affected by bicuculline pretreatment, but strychnine (i.c.v) prevented the effects of taurine. These findings indicate that glycine-type receptors may be involved in the taurine effects rather than gamma-aminobutyric acid type receptors. However, these results do not exclude the involvement of taurine-type receptors for which the specific antagonists is not yet available.

Abstract: High resolution electron microscopy of ultrathin sections confirms the presence of a membrane surrounding the tapetal rods in the cat. Cats depleted of taurine exhibit disruption and disorganization of this membrane, probably the first stage of more severe tapetal degeneration. Histochemical localization of zinc shows it to be present on the periphery of the tapetal rods. The amount of zinc present on the periphery of the tapetal rods of taurine depleted cats was greatly reduced. Taurine in feline tapetum, confirmed by autoradiography and direct measurement, was also greatly reduced in taurine-depleted cats. We conclude that both taurine and zinc are localized on the periphery of the tapetal rods and that they contribute to the stability of the membrane. We have also confirmed earlier reports that the cat tapetal rods contain riboflavin and no detectable cysteine.

Abstract: In neuroblastoma x glioma hybrid cells, a cell line of neuronal character, a saturable uptake system for taurine is found which displays high affinity and high capacity (km = 38 micro M, V = 1.25 nmol . mg-1 . min-1). Only the closely related structural analogues hypotaurine and beta-alanine are able to inhibit the transport of radioactively labeled taurine. Imipramine or haloperidol at 100 micro M effectively blocks taurine uptake. High-affinity taurine uptake shows an absolute and highly specific requirement for Na+. The hybrid cells internalize taurine very slowly and, with 1 mM extracellular taurine, attain a plateau only after more than 20 h, at which time approximately 34 mM labeled taurine has accumulated in the cytosol. Generally there is hardly any spontaneous release of accumulated taurine. Efflux can, however, be induced by increasing the intracellular Na+ content and is then accelerated by lowering the extracellular Na+ concentration. The hypothesis is forwarded that taurine may exert its function by driving the extrusion of Na+ in emergency situations.

Abstract: Infant mice (2 to 4 days old) received valproate (100 or 200 mg per kilogram body weight) subcutaneously once daily for 5 days. Both dosages decreased plasma beta-hydroxybutyrate levels to about one-third of the control value, in the face of normal free fatty acid and glycerol levels. At 200 mg per kilogram of valproate, there were significant decreases in brain weight and brain K content. Both doses produced metabolite changes in brain compatible with a reduced metabolic flux through the glycolytic pathway and the citric acid cycle. Valproate reduced brain aspartate but did not increase brain GABA levels in infant mice. At 200 mg per kilogram of valproate, brain glutamate decreased and taurine levels increased. Two hundred milligrams per kilogram of valproate caused a profound reduction of liver glycogen stores. The apparent decrease in cerebral metabolic rate, reduced glutamate and aspartate, and increased levels of taurine in brain may relate to the anticonvulsant action of valproate. Together with the decreased brain weight and K content, the findings are also compatible with maturational delay. Decreased ketonemia and liver glycogen content may relate to the hepatic toxicity associated with valproate administration in infants and children.

Abstract: Isolated frog rod outer segments (ROS) incubated in a Krebs-bicarbonate medium, and illuminated for 2 h, show a profound alteration in their structure. This is characterized by distention of discs, vesiculation, and a marked swelling. The light-induced ROS disruption requires the presence of bicarbonate and sodium chloride. Replacement of bicarbonate by TRIS or HEPES protects ROS structure. Also, substitution of sodium chloride by sucrose or choline chloride maintains unaltered the ROS structure. Deletion of calcium, magnesium, or phosphate does not modify the effect produced by illumination. An increased accumulation of labeled bicarbonate and tritiated water is observed in illuminated ROS, as compared with controls in the dark. The presence of taurine, GABA, or glycine, at concentrations of 5-25 mM, effectively counteracts the light-induced ROS disruption. Taurine (25 mM) reduces labeled bicarbonate and tritiated water levels to those observed in the dark incubated ROS.

Abstract: The quantitative importance of the mother as a source of taurine for neonatal rats has been examined by maintaining female rats on a diet contain ing 3H-taurine until they were uniformly labeled, and then mating them. Rats were kept on the 3H-taurine diet throughout pregnancy and lactation. The trans fer of taurine from the mother to the pup both in utero and during nursing could thus be followed, and the quantity of taurine biosynthesized by the pup cal culated. Pups were weaned at 21 days of age onto either a taurine-free diet or a diet containing 0.4% of non-radioactive taurine. The loss of 3H-taurine from various organs was followed. Whole body half-life of 3H-taurine was 11.4 days from rats fed the taurine-enriched diet and 15.0 days for rats on the taurine-free diet. Regardless of the diet, internal organs and the brain had faster rates of turn over than turnover from the muscle or from the whole animal. Both groups showed the same increase in total body taurine in the 4 weeks after weaning, indicating that young rats can biosynthesize considerable quantities of taurine. J. Nutr. Ill: 1275-1286, 1981.

Abstract: Hypotaurine uptake was compared to taurine and GABA uptakes in brain slices under identical experimental conditions. The slices effectively concentrated both hypotaurine and GABA from the medium, whereas taurine was taken up more slowly. The uptakes of these three structurally related amino acids were all saturable, consisting of one low-and one high-affinity transport component. The kinetic parameters of hypotaurine uptake were of the same order of magnitude as those of GABA uptake. All uptake systems were sensitive to temperature, metabolic poisons, and sodium omission. Hypotaurine uptake was inhibited by GABA,l-2,4-diaminobutyric acid (l-DABA), cysteic acid, and β-alanine, but not by taurine. Taurine uptake was strongly reduced by hypotaurine, β-alanine, andl-DABA, as well as by GABA, whereas GABA uptake was affected only by cystamine,l-DABA, and nipecotic acid. The uptake processes of hypotaurine, taurine, and GABA were thus fairly similar and showed properties characteristic for neurotransmitter uptake. Hypotaurine uptake resembled more GABA than taurine uptake. The present inhibition studies suggest that there may exist only one common two-component transport system for these three amino acids.

Abstract: The intracerebroventricular (i.c.v.) injection of taurine produced a fall in core temperature, the extent of which was dependent on the thermal gradient between the body and the environment. Concurrently, a sudden rise in ear skin temperature, which was maximal in the cold and negligible at 30 degrees C, was observed. The fever induced by i.v. injection of Escherichia coli endotoxin was antagonized by taurine. High temperatures produced by i.c.v. injection of prostaglandin E1 were also suppressed by taurine. Intracerebroventricular injections of bicuculline and strychnine, but not those of picrotoxin or pentylentetrazol, were able to reduce hypothermia induced by taurine. Intracerebroventricular injection of the taurine reuptake inhibitor guanidinoethyl sulfonate, on the contrary, did enhance the hypothermic response to taurine. Injection (i.c.v.) of serotonin (5-HT) elicited a fall in core temperature which was not accompanied by a rise in ear skin temperature, but was antagonized by the concurrent injection of the 5-HT antagonist methysergide. Pretreating animals with p-chlorophenyl-alanine caused a significant fall of brain 5-HT contents and a reduction of the hypothermic response to taurine. The latter effect was also observed when the animals were i.c.v. pretreated either the methysergide or with the 5-HT reuptake blockers chlorimipramine and Lilly 110140. These findings give support to the hypothesis that taurine-induced hypothermia in rabbits mediated by some taurine sensitive cells and, at least in part, by serotonergic synaptic mechanisms.