Abstract: 1. Taurine sensitive receptors in the antennules of the spiny lobster, Panulirus argus, were identified electrophysiologically.2. Recordings from single receptors revealed a narrow and consistent specificity when tested with taurine, taurine analogs and derivatives, and structurally related compounds.3. Taurine was the most stimulatory compound tested. Threshold concentrations for 36 individual receptors ranged from 10-8 to 10-10 M.4. The taurine analogs, hypotaurine and β-alanine, were also very effective but the phosphonic acid analog of taurine was ineffective.5. Regarding receptor specificity, receptor stimulation was greatest with compounds having single terminal basic (amine) and acidic groups separated by two carbon atoms. Compounds having terminal basic and acidic groups separated by three to five carbon atoms were also active. However, activity decreased with the distance of separation of charged groups.6. Alpha-amino acids and compounds with terminal basic and acidic groups separated by only one...

Abstract: 1 Records of ventral and dorsal root polarity of the isolated hemisected spinal cord of the 3-9 day old rat showed that respective dose-dependent depolarizations of motoneurones (VR responses) and primary afferent terminals (DR responses) were produced by both acidic and neutral amino acids in the presence of procaine (1 mM) or tetrodotoxin (0.1 micron). 2 Of the four neutral amino acids, gamma-aminobutyrate (GABA), glycine, taurine, and beta-alanine, GABA was the most effective in producing DR responses and glycine the most effective in producing VR responses. Only taurine depressed the electrical activity recorded from ventral roots. 3 The DR responses produced by GABA, beta-alanine and taurine were all antagonized by bicuculline (5 micron) and picrotoxin (5 micron). Bicuculline was more selective than picrotoxin in antagonizing VR responses produced by GABA. 4 Strychnine (1 micron) antagonized VR responses produced by glycine beta-alanine and taurine without affecting responses produced by GABA. DR responses to the neutral amino acids were unaffected by strychnine.

Abstract: Kittens fed a purified diet containing partially-purified casein as the source of protein become taurine-deficient and develop retinal degeneration. The present studies report the exchange and turnover of taurine in different areas of brain, retina and other tissues and fluids of control and taurine-deficient kittens. The various tissues and fluids have different rates of exchange and different half-lives of taurine; taurine deficiency causes a range of changes in these parameters. Generally, tissues and fluids from taurine-deficient kittens accumulated more [35S] taurine and had a longer half-life of taurine than tissues and fluids from control kittens. Nine areas of brain were studied and, of these areas, olfactory bulb had the greatest concentration of taurine. Olfactory bulb resisted taurine depletion to a greater extent than other areas; and, in contrast to other areas of brain, in taurine-deficient kittens, it accumulated [35S] taurine for most of the experiment. Retina resisted taurine depletion and, in taurine-deficient kittens but not in control kittens, it accumulated [35S] taurine throughout the experiment. The amount of taurine conjugated to bile acids was unchanged by the taurine depletion, but the kinetic behavior was altered and was similar to that of retina. The results provide support for the suggestion that, in the kitten at least, taurine is most important for the functions of bile and retina and that taurine depletion affects retina before bile. Taurine may have special importance in olfactory bulb but not necessarily in other regions of brain.

Abstract: — Brain amino acids were measured in rats given aminooxyacetic acid (AOAA) by mouth, and in rats given sodium dipropylacetate (DPA) both orally and by intraperitoneal injection. Brain GABA content was significantly elevated by AOAA doses of 10mg/kg/day, but not by 5mg/kg/day. Approximately 4 times as much AOAA is required by mouth as by parenteral injection to raise brain GABA content in the rat. DPA (400mg/kg) increased brain GABA and lowered brain aspartate content significantly 1 h after a single injection. However, DPA given orally (350 mg/kg/day) produced no alterations of any amino acids in rat brain. Amino acids were measured in plasma and urine from patients treated orally with isonicotinic acid hydrazide (INH) or DPA, and from a volunteer who took AOAA. INH (10–21 mg/kg/day) increased concentrations of β-alanine and ornithine in plasma, as well as urinary excretion of β-alanine. DPA had no such effect. AOAA in oral doses ranging from 1.25 to 5.0 mg/kg/day increased plasma concentrations of β-alanine, ornithine, β-aminoisobutyric acid, proline and hydroxyproline, and produced massive urinary excretion of β-alanine, β-aminoisobutyric acid, and taurine. Both INH and AOAA, given in doses practical for human use, inhibit the transamination of β-alanine and ornithine in liver, and may also inhibit the transamination of GABA in brain. In addition, AOAA interferes with the catabolism of β-aminoisobutyric acid, proline, and hydroxyproline. AOAA, in the lowest dose employed, appeared more effective than INH as an inhibitor of GABA aminotransferase in man, and might therefore be useful in the treatment of neurological diseases in which brain GABA is deficient.

Abstract: Sodium-dependent transport of taurine into rat brain synaptosomes was studied using [3H]taurine of high specific activity (2.8 Ci/mmole). At 2.8 µM [3H]taurine, 57% of the total radioactive accumulation was directly proportional to the sodium ion concentration. The sodium-dependent, high-affinity transport was a linear function of added protein and incubation length, and was maximal between pH 6.6 and 8.6. Kinetic analyses indicated a high-affinity apparent Km value of 4.76 µM and an apparent Vmax value of 5.35 nmoles/g of protein per minute. After correction of the high-affinity transport for that portion contributed by the low-affinity system, the true kinetic constants of the high-affinity system were calculated to be 3.20 µM and 2.96 nmoles/g of protein per minute. Similarly, the true kinetic constants of the low-affinity system were calculated to be 3340 µM and 699 nmoles/g of protein per minute. The Hill plot for both the high- and low-affinity transport systems had a slope of about 1, which suggested a 1:l interaction between taurine and its transport molecule. The sodium-dependent, high-affinity transport of [3H]taurine was decreased by the removal of potassium or chloride ions, and was absent from lysed synaptosomes or when the assay was performed at 2°. The omission of glucose or the addition of dinitrophenol slightly reduced transport. Ouabain inhibited transport in a time- and dose-dependent manner. The Arrhenius plot of [3H]taurine transport revealed an energy of activation (Ea) of 15.6 kcal/mole and an energy quotient (Q10) of 2.34, each of which indicated an active process. The regional distribution of uptake showed that the midbrain, thalamus, and olfactory bulbs had the highest velocity of transport, while the cerebral cortex, spinal cord, and cerebellum had the lowest velocity of transport. Several structural analogues were inhibitors of taurine transport, and analyses of structure-activity relationships revealed that the uptake site was very specific. Only molecules with free anionic and cationic groups were potent inhibitors. These data are consistent with the hypothesis that taurine is a neurotransmitter or neuromodulator in the brain, and we have investigated some of the molecular characteristics of this transport.

Abstract: — It was found that rat brain nerve endings contain a high affinity and Na- dependent transport system for [3H]β-alanine ([3H]β-ala). As determined from Michaelis-Menten plots, the [3H]β-ala Km was 2.8 × 10-5 M and the Vmax was 0.29 nmol/mg protein/5 min. Under similar incubation conditions the [3H]GABA Km was 3.8 x 10-6M and the Vmax was 6.3 nmol/mg protein/5 min. The [3H]β-ala and [3H]GABA transport systems were further characterized by determining the IC50 values for a number of compounds. The compounds tested were GABA, β-ala, l-2,4-diaminobutyric acid. DL-3-hyd-roxy-GABA, β-guanidopropionic acid, strychnine, γ-guanidobutyric acid, imidazole-4-acetic acid, DL-proline, bicuculline, L-serine, glycine, l-α-ala and taurine. DABA, dl-3-hydroxy-GABA, β-guanidopro-pionic acid and γ-guanidobutyric acid were more potent inhibitors of [3H]GABA than [3H]β-ala transport. Strychnine, imidazole-4-acetic acid, proline and glycine were between 2 and 6 times more potent inhibitors of [3H]β-ala than [3H]GABA transport. β-Ala, bicuculline, serine, α-alanine and taurine were all markedly more potent (12–150 times) inhibitors of [3H]β-ala than [3H]GABA transport. IC50 values were also determined for the above compounds for the sodium-dependent and the sodium-independent binding of [3H]GABA to both fresh and frozen brain membranes. In general, the potency of these compounds to inhibit either sodium-independent or sodium-dependent binding was greater in fresh tissue. It was also observed that the neurophysiologically‘glycine-like’amino acids were more potent inhibitors in the presence of NaCl. No significant correlations were found between [3H]GABA binding under any condition and [3H]GABA or [3H]β-ala transport into nerve endings.

Abstract: Subcutaneous administration of high doses of sodium glutamate to new born rats was used to destroy retinal interneurons and ganglion cells. Such treatment was accompanied by 90% reduction in the high affinity uptake of choline, 60–70% reductions in the uptakes of GABA, diamino-n-butyric acid and glycine and 30–40% reductions in the uptakes of asparatate and glutamate measured on retinal homogenates from 30-day-old rats. The high affinity uptakes of β-alanine and taurine were unchanged. Preincubation of retinal homogenates with 1 mM β-alanine or 100 μM diamino-n-butyric acid severely reduced the high affinity GABA uptake in control and experimental animals. In intact retinae, however, the glutamate treatment increased the high affinity uptake of β-alanine by 70%, whereas that of diamino-n-butyric acid was reduced by 40% and the high affinity uptakes of GABA and glutamate were unchanged. Four hours after injection of the gliotoxic compound DL-α-aminoadipic acid into the vitreous body of 30-day-old rats, the Muller cells could no longer be identified. This lesion was accompanied by 55% reduction in the high affinity uptake of β-alanine and 25% reduction in the uptakes of GABA and glutamate on intact retinae. The high affinity uptakes of diamino-n-butyric acid, choline and the enzyme activities of choline acetyltransferase and glutamate decarboxylase were unchanged under these conditions. After 24 h, however, the Muller cells could be recognized again, and the β-alanine uptake had normalized.

Abstract: Taurine, a putative inhibitory neurotransmitter, was injected in various doses intracerebroventricularly to conscious rats via pre-implanted polythene cannulas. The formation of DOPA and 5-hydroxytryptophan (5-HTP) in various brain regions was investigated by measuring the accumulation of these monoamine precursors induced within 30 min by the intraperitoneal injection of 3-hydroxybenzyl hydrazine HCl (NSD 1015, 100 mg/kg), an inhibitor of the aromatic L-amino acid decarboxylase readily penetrating into the brain. DIPA formation, but not 5-HTP formation was significantly enhanced by taurine in dose-related manner in all brain regions studied, indicating an increased synthesis of both dopamine and noradrenaline. Dopamine depletion induced by α-methyltyrosine was significantly retarded by taurine, whereas noradrenaline depletion tended to be enhanced. Endogenous levels of dopamine were increased, whereas the following brain constituents were unchanged: tyrosine, tryptophan, noradrenaline, 5-HT and 5-hydroxyindoleacetic acid. In the exoeriments with NSD 1015, a dose-related decrease in rectal temperature and in motility was observed after taurine treatment, as compared to treatment with the decarboxylase inhibotor alone. Systemic parenteral administration of taurine caused no significant changes in brain monoamines, body temperature or behaviour but decreased the heart noradrenaline levels. The data indicate that taurine, which apparently has to be given intracerebroventricularly in order to reach the brain in sufficient amounts, causes inhibition of firing in central dopamine neurons but has the opposite effect on noradrenaline neurons, perhaps also peripherally, whereas 5-HT neurons appear to be unaffected. In addition, taurine appears to interfere with motor behaviour and temperature regulation, possibly via effects on catecholaminergic systems.

Abstract: In order to elucidate the flavor components characteristic of boiled crabs, the suitable method of extraction was examined and extracts were prepared from different edible parts of five species of crab. The amino acid composition of the extracts was analyzed as the first step of a series of of investigations on the flavor components. A common feature of the free amino acid composition of the leg meat extracts was a very high content of glycine and arginine, with somewhat lower amounts of proline and taurine; the former two comprised about 50% of the total of free amino acids. In the extracts of the hepatopancreas and ovary, the abundant amino acids were taurine, glycine, and arginine. After acid hydrolysis of the extracts, the total of free amino acids showed a 10-20% increase in the leg meat and the ovary and a 50-70% increase in the hepatopancreas, The main amino acids to increase were glutamic and aspartic acids.

Abstract: Sixteen isonitrogenous, isoenergetic diets were fed to fingerling channel catfish to study the efficacy of L-methionine, DL-methionine, methionine hydroxy analogue (OH-M), taurine and sodium sulfate. The basal diet contained casein and gelatin supplemented with crystalline L-amino acids to correspond to the amino acid pattern found in 24% crude protein from whole egg powder. The basal diet, containing 0.26% methionine was supplemented with graded levels of each of the sulfur sources on an isosulfurous basis. Growth and feed efficiency data indicate that channel catfish can utilize DL-methionine as effectively as L-methionine. OH-M was only about 26% as effective in promoting growth as L-methionine. No significant growth response was observed when taurine or inorganic sulfate was added to the basal diet.

Abstract: The effect of depolarizing potassium concentration on the release of [14C]glycine, [3H]GABA, and [35S]taurine was investigated in the whole chick retina and in a synaptosomal fraction prepared from the chick retina. In the whole retina, increasing potassium concentration above 40 mM resulted in an increased release of the three amino acids. The release of glycine was the most stimulated and that of taurine, the least. The potassium-evoked release of glycine and GABA was calcium dependent. In the synaptosomal fraction, 68.5 mM potassium significantly stimulated the efflux of GABA and glycine by a calcium-dependent mechanism. The release of taurine from this fraction was unaffected by high potassium.

Abstract: The size and composition of the bile-salt pools in a group of diabetics with neuropathy but no diarrhoea and a group with "diabetic diarrhoea" were compared with those in a group of stable, uncomplicated diabetics. The diabetics with neuropathy had significantly more dihydroxy bile salts, a larger bile-salt pool, and a higher faecal excretion of bile than the controls. The diabetics with diarrhoea had significantly more dihydroxy bile salts, a higher glycine to taurine ratio, a smaller bile-salt pool, and increased excretions of 14C-tracer and total bile salts. We conclude that considerable alterations occur in the bile of diabetics with neuropathy or diarrhoea, and we suggest that in some cases at least these abnormalities may indicate a mechanism for diabetic diarrhoea.

Abstract: SummaryThe effects of cellular hypoxia on taurine levels in rat hearts were determined. Hearts perfused with 95% N2-5% CO2 demonstrated a significant decrease in tissue taurine content when compared to control hearts perfused with 95% O2-5% CO2. The loss of taurine in oxygen-deficient hearts was time dependent over a period of 30 min. The perfusate when analyzed for taurine content contained 100% of the released taurine. Thus, metabolic conversion of taurine had no role in the disappearance of taurine from the rat heart.

Abstract: — GABA, taurine and β-alanine are taken up by guinea-pig cerebellar slices by both the high-and low-affinity uptake processes, whereas glycine is taken up only by the low-affinity process. A considerable amount of labelled GABA loaded in the slice is released by unlabelled external GABA and a minute amount is released by external β-alanine, glycine and taurine. External glycine and β-alanine releases labelled glycine loaded in the slice. Labelled taurine loaded is effectively released by external taurine and β-alanine, while labelled β-alanine loaded is released only by external β-alanine. It is suggested that hetero-exchanges which are one-directional in some cases also take place between the amino acids in addition to homo-exchanges. Therefore, high-affinity uptake processes observed with GABA and taurine could be the result of the homo-exchange diffusions, while that of β-alanine could be due to either the homo-exchange or the hetero-exchange diffusions or both. K+′-evoked releases of GABA and to a lesser extent, taurine are partially dependent upon the presence of Ca+ in the superfusion media, whereas that of glycine and probably that of β-alanine, are not, K+ -evoked releases of labelled GABA and taurine are larger when loaded by their high-affinity uptake systems than by their low-affinity uptake processes. The reverse is the case with labelled glycine and β-alanine. These results do not rule out the possibility that taurine might act as a neurotransmitter in the cerebellum.