Suppression of conditioned drinking by taurine and related compounds.

Mice were conditioned to respond for water reinforcements on a FR-5 schedule. Taurine, injected intraperitoneally at doses of 9.0, 13.8, and 21.3 mmole/kg 30 min prior to the experimental session, produced a dose-related decrease in both the initial response rate and total number of reinforcements received by mice deprived of water for 24 hr. The structural analogues of taurine (aminomethanesulfonic acid, 3-aminopropanesulfonic acid, beta-alanine, cysteamine, and glycine) also produced a hypodipsia. Doses of taurine which produced depression of responding for water reinforcements were used which produced no suppression of spontaneous motor activity, rotarod performance, Sidman avoidance, or shuttle-box avoidance. After intraperitoneal injection, the concentration of taurine increased in the hypothalamus and medulla, but not in other brain areas. We suggest that taurine might be acting by specifically depressing areas of the hypothalamus which stimulate drinking.     

Taurine and hypotaurine transport by a single system in cultured neuroblastoma cells

The kinetics of mutual inhibition of taurine and hypotaurine uptake were studied using neuroblastoma C1300 cells as neuronal model. Hypotaurine and GABA inhibited taurine uptake competitively, increasing the apparent K_m. High-affinity uptake of hypotaurine was completely abolished and the low-affinity component competitively inhibited by taurine. GABA affected noncompetitively low-affinity hypotaurine uptake, whereas the effect on high-affinity uptake was competitive, with an increase in the apparent K_m. All structural analogues tested inhibited taurine and hypotaurine uptakes similarly. The most potent inhibitors were β-alanine and 2-guanidinoethanesulphonic acid. The mutual inhibition and similar specificity profiles of taurine and hypotaurine uptakes showed that these amino acids employ a single transport system in neuroblastoma cells. Competitive inhibition by GABA of the high-affinity uptake of taurine and hypotaurine further suggests that also GABA uses the same carrier system.     

Effect of electrical stimulation on the influx and efflux of taurine in brain slices of newborn and adult rats

Summary Brain slices from adult and newborn rats were incubated with [³⁵S]taurine in Krebs-Ringer bicarbonate medium at pH 7.4. In both age groups electrical stimulation increased the oxygen consumption of the slices. The influx of taurine only increased in slices from adult rats. The influx conformed to Michaelis-Menten kinetics. In slices from adult rat V_max increased and apparent K_m remained unchanged during electrical stimulation. Both K_m and V_max were greater in adult than in newborn rats. The efflux of taurine from slices depended on the intracellular concentration of taurine and was not measurably influenced by electrical stimulation.     

Effects of Taurine and Taurine Analogues on the Phosphorylation of a 44 kDa Protein Present in a Mitochondrial Subfraction of the Rat Heart: Partial Characterization of the 44 kDa Phosphoprotein

Recent studies suggest that taurine (2-aminoethanesulfonic acid) is involved in the regulation of protein phosphorylation in excitable tissues such as the retina, brain and heart. In order to determine the structural requirements for the effect of taurine on the phosphorylation of a 44 kDa protein(s), a series of taurine analogues were tested in an in vitro assay using a subcellular mitochondrial fraction of rat heart. Inhibitors of the phosphorylation of the 44 kDa protein include taurine and close structural analogues of taurine such as aminoethylhydrogen sulfate and α-sulfo-β-alanine. Secondary amines with the taurine structure partially locked into a saturated 5-membered ring such as (±) piperidine-3-sulfonic acid and 1,2,3,4-tetrahydroquinoline-8-sulfonic acid also possess inhibitory activity. Sulfone analogues of taurine such as 2-aminoethylmethylsulfone, a non-restricted taurine analogue with maximal conformational flexibility about its amino and sulfone moieties, and (±) 3-aminotetrahydrothiopyran-1.1-dioxide, an analogue containing the sulfone moiety in a six-membered ring structure, were found to be more potent inhibitors of phosphorylation than taurine despite the fact that the sulfone moiety is neither an isosteric nor isoelectronic substitution for the sulfonic acid moiety. The results of this study indicate that the inhibition of the phosphorylation of the 44 kDa protein in a rat heart mitochondrial fraction is relatively specific for the taurine structure. Two analogues of taurine with unsaturated rings containing a primary sulfonic acid and a secondary amine, pyridine-3-sulfonic acid and quinoline-8-sulfonic acid, were observed to be stimulators of the phosphorylation of the 44 kDa protein. In addition, 2-aminobenzenesulfonic acid also stimulated phosphorylation. Phase separation experiments with Triton X-114 suggest that the 44 kDa phosphoprotein is a soluble protein and not an integral membrane protein of the mitochondria. Phosphate incorporation into specific amino acids was determined by two-dimensional electrophoresis on celluloses plates and was found exclusively in the serine residues.     

Taurine allosterically inhibits binding of [S]-t-Butylbicyclophosphorothionate (TBPS) to rat brain synaptic membranes

The modulatory effects of taurine on [³⁵S]-t-Butylbicyclophosphorothionate (TBPS) binding to rat brain synaptic membranes were evaluated and compared with that of GABA. Taurine allosterically inhibited TBPS binding by interacting with a bicuculline-sensitive site, similar to GABA. Taurine was as effective as GABA but less potent. The potency of taurine inhibition of TBPS binding varied among brain regions with cerebellum > olfactory bulb > cortex, similar to that of GABA. Inhibition of TBPS binding to cortical membranes measured under nonequilibrium conditions yielded a dynamic biphasic inhibition curve that was similarly shaped for GABA and taurine. The effect of taurine on TBPS binding was pharmacologically specific in that β-alanine and guanadinoethanesulfonate were as effective as taurine, while hypotaurine and -aminoethylhydrogen sulfate were only partially effective at high concentrations, and isethionic acid was without effect. Taurine, similar to GABA enhanced the effects of pentobarbital on TBPS binding when present at concentrations that were otherwise ineffective on their own. The results of these studies support the notion that taurine interacts with the GABA recognition site of the GABA_A receptor complex.     

Effects of Taurine on Kindled Amygdaloid Seizures in Rats, Cats, and Photosensitive Baboons

Acute administration of taurine produced a transient loss of susceptibility to photically induced seizures in photosensitive baboons, but failed to affect kindled amygdaloid convulsions in baboons, rats, and cats. In addition, it was totally ineffective in changing the course of spontaneous status epilepticus in kindled cats. These results suggest that a taurine-deficiency model of epilepsy applies only to certain types of seizure-generating conditions, apparently excluding kindled amygdaloid convulsions.     

Effect of taurine on calcium kinetics of guinea-pig heart

Guinea-pig hearts, perfused with Tyrode containing 8 mM taurine, show a less marked decrease of contractile force when washed out with calcium-free Tyrode than control hearts. The effects of taurine cardiac contractility are explained by its interference with calcium kinetics. Total calcium content is increased in taurine-treated hearts, and greater amounts of calcium are washed out from calcium exchanging compartments, analyzed according to the model of Bayley et al. (1968). Most of the additional calcium retained by taurine-treated hearts is bound to some tissue structure, and can be partially mobilized when the concentration of easily exchanged calcium falls. The hypothesis is advanced that taurine increases the affinity of some cell structure for calcium.     

牛磺酸和维生素E对高脂家兔血清锌,铜,铁,钙的影响

本文研究了牛横酸和维生素Ｅ对饲高脂家兔血清锌，铜，铁，钙的影响。结果表明，牛磺酸能显著增加高脂家兔出血清锌含量（Ｐ＜０．０５），而维生素Ｅ显著降低高脂家兔血清铜含量（Ｐ＜０．０１）。总的牛磺酸和维生素Ｅ都非常显著地降低了高脂家兔的血清铜／锌比值（Ｐ＜０．０１），对血清铁和钙无显著性影响。提示牛横酸和维生素Ｅ可能通过调节体内的锌，铜代谢而影响脂质代谢及动脉粥样硬化形成。     

Neuroactive amino acids in the area postrema

Summary The localization of five neuroactive amino acids in the rat area postrema was studied by postembedding immunocytochemistry in semithin and ultrathin sections. Antisera to GABA, glycine, glutamate and aspartate produced labelling of cells that were identified as neurons in the electron microscope. GABA-like and glycine-like immunoreactivities occurred in about 20% and 60% of the neurons, respectively, and a minor proportion of the cells displayed both immunoreactivities, suggesting a cellular colocalization of GABA and glycine. Immunoreactivities for glutamate and aspartate were found in a large majority of the neurons, including most of the cells that were positive for GABA and/or glycine. Taurine immunoreactivity was highly concentrated in a few small cells with ultrastructural features typical of microglial cells, and in processes that were probably derived from these. Taurine also appeared to be abundant in cells confined to the perivascular space. The electron microscopic, immunogold analysis of the neuropil revealed numerous nerve terminals that were enriched in GABA or glutamate immunoreactivity, compatible with a transmitter role of these amino acids. Glycine immunolabelling was found preferentially in post-synaptic elements, suggesting that the glycine-containing cells lack locally ramifying axon collaterals, and that they mainly project outside the area postrema. Aspartate immunolabelling was also generally low in axon terminals. This is similar to the situation in several other brain areas and could indicate that the latter amino acid primarily serves metabolic functions in the area postrema.