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1.
Summary. Taurine has been thought to be essential for the development and survival of neural cells and to protect them under cell-damaging
conditions. In the brain stem taurine regulates many vital functions, including cardiovascular control and arterial blood
pressure. We have recently characterized the release of taurine in the adult and developing brain stem under normal conditions.
Now we studied the properties of preloaded [3H]taurine release under various cell-damaging conditions (hypoxia, hypoglycemia, ischemia, the presence of metabolic poisons
and free radicals) in slices prepared from the mouse brain stem from developing (7-day-old) and young adult (3-month-old)
mice, using a superfusion system. Taurine release was greatly enhanced under these cell-damaging conditions, the only exception
being the presence of free radicals in both age groups. The ischemia-induced release was characterized to consist of both
Ca2+-dependent and -independent components. Moreover, the release was mediated by Na+-, Cl−-dependent transporters operating outwards, particularly in the immature brain stem. Cl− channel antagonists reduced the release at both ages, indicating that a part of the release occurs through ion channels,
and protein kinase C appeared to be involved. The release was also modulated by cyclic GMP second messenger systems, since
inhibitors of soluble guanylyl cyclase and phosphodiesterases suppressed ischemic taurine release. The inhibition of phospholipases
also reduced taurine release at both ages. This ischemia-induced taurine release could constitute an important mechanism against
excitotoxicity, protecting the brain stem under cell-damaging conditions. 相似文献
2.
Summary. Taurine has been thought to function as a regulator of neuronal activity, neuromodulator and osmoregulator. Moreover, it is
essential for the development and survival of neural cells and protects them under cell-damaging conditions. Taurine is also
involved in many vital functions regulated by the brain stem, including cardiovascular control and arterial blood pressure.
The release of taurine has been studied both in vivo and in vitro in higher brain areas, whereas the mechanisms of release
have not been systematically characterized in the brain stem. The properties of release of preloaded [3H]taurine were now characterized in slices prepared from the mouse brain stem from developing (7-day-old) and young adult
(3-month-old) mice, using a superfusion system. In general, taurine release was found to be similar to that in other brain
areas, consisting of both Ca2+-dependent and Ca2+-independent components. Moreover, the release was mediated by Na+-, Cl−-dependent transporters operating outwards, as both Na+-free and Cl− -free conditions greatly enhanced it. Cl− channel antagonists and a Cl− transport inhibitor reduced the release at both ages, indicating that a part of the release occurs through ion channels.
Protein kinases appeared not to be involved in taurine release in the brain stem, since substances affecting the activity
of protein kinase C or tyrosine kinase had no significant effects. The release was modulated by cAMP second messenger systems
and phospholipases at both ages. Furthermore, the metabotropic glutamate receptor agonists likewise suppressed the K+-stimulated release at both ages. In the immature brain stem, the ionotropic glutamate receptor agonists N-methyl-D-aspartate
(NMDA) and 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) potentiated taurine release in a receptor-mediated manner.
This could constitute an important mechanism against excitotoxicity, protecting the brain stem under cell-damaging conditions. 相似文献
3.
Summary. Glutathione (reduced form GSH and oxidized form GSSG) constitutes an important defense against oxidative stress in the brain,
and taurine is an inhibitory neuromodulator particularly in the developing brain. The effects of GSH and GSSG and glycylglycine,
γ-glutamylcysteine, cysteinylglycine, glycine and cysteine on the release of [3H]taurine evoked by K+-depolarization or the ionotropic glutamate receptor agonists glutamate, kainate, 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionate
(AMPA) and N-methyl-D-aspartate (NMDA) were now studied in slices from the hippocampi from 7-day-old mouse pups in a perfusion system.
All stimulatory agents (50 mM K+, 1 mM glutamate, 0.1 mM kainate, 0.1 mM AMPA and 0.1 mM NMDA) evoked taurine release in a receptor-mediated manner. Both
GSH and GSSG significantly inhibited the release evoked by 50 mM K+. The release induced by AMPA and glutamate was also inhibited, while the kainate-evoked release was significantly activated
by both GSH and GSSG. The NMDA-evoked release proved the most sensitive to modulation: L-Cysteine and glycine enhanced the
release in a concentration-dependent manner, whereas GSH and GSSG were inhibitory at low (0.1 mM) but not at higher (1 or
10 mM) concentrations. The release evoked by 0.1 mM AMPA was inhibited by γ-glutamylcysteine and cysteinylglycine, whereas
glycylglycine had no effect. The 0.1 mM NMDA-evoked release was inhibited by glycylglycine and γ-glutamylcysteine. In turn,
cysteinylglycine inhibited the NMDA-evoked release at 0.1 mM, but was inactive at 1 mM. Glutathione exhibited both enhancing
and attenuating effects on taurine release, depending on the glutathione concentration and on the agonist used. Both glutathione
and taurine act as endogenous neuroprotective effectors during early postnatal life.
Authors’ address: Prof. Simo S. Oja, Brain Research Center, Medical School, FI-33014 University of Tampere, Finland 相似文献
4.
Taurine and neural cell damage 总被引:22,自引:2,他引:20
Summary. The inhibitory amino acid taurine is an osmoregulator and neuromodulator, also exerting neuroprotective actions in neural
tissue. We review now the involvement of taurine in neuron-damaging conditions, including hypoxia, hypoglycemia, ischemia,
oxidative stress, and the presence of free radicals, metabolic poisons and an excess of ammonia. The brain concentration of
taurine is increased in several models of ischemic injury in vivo. Cell-damaging conditions which perturb the oxidative metabolism
needed for active transport across cell membranes generally reduce taurine uptake in vitro, immature brain tissue being more
tolerant to the lack of oxygen. In ischemia nonsaturable diffusion increases considerably. Both basal and K+-stimulated release of taurine in the hippocampus in vitro is markedly enhanced under cell-damaging conditions, ischemia,
free radicals and metabolic poisons being the most potent. Hypoxia, hypoglycemia, ischemia, free radicals and oxidative stress
also increase the initial basal release of taurine in cerebellar granule neurons, while the release is only moderately enhanced
in hypoxia and ischemia in cerebral cortical astrocytes. The taurine release induced by ischemia is for the most part Ca2+-independent, a Ca2+-dependent mechanism being discernible only in hippocampal slices from developing mice. Moreover, a considerable portion of
hippocampal taurine release in ischemia is mediated by the reversal of Na+-dependent transporters. The enhanced release in adults may comprise a swelling-induced component through Cl− channels, which is not discernible in developing mice. Excitotoxic concentrations of glutamate also potentiate taurine release
in mouse hippocampal slices. The ability of ionotropic glutamate receptor agonists to evoke taurine release varies under different
cell-damaging conditions, the N-methyl-D-aspartate-evoked release being clearly receptor-mediated in ischemia. Neurotoxic
ammonia has been shown to provoke taurine release from different brain preparations, indicating that the ammonia-induced release
may modify neuronal excitability in hyperammonic conditions. Taurine released simultaneously with an excess of excitatory
amino acids in the hippocampus under ischemic and other neuron-damaging conditions may constitute an important protective
mechanism against excitotoxicity, counteracting the harmful effects which lead to neuronal death. The release of taurine may
prevent excitation from reaching neurotoxic levels.
Received January 25, 2000/Accepted January 31, 2000 相似文献
5.
The novel neurotransmitter/neuromodulator nitric oxide (NO), which is linked to the activation of the N-methyl-D-aspartate class of glutamate receptors, has been shown to modify transmitter release in brain tissue. Release of the inhibitory amino acid taurine is also markedly enhanced by N-methyl-D-aspartate and NO-producing agents under normal conditions in the mouse hippocampus. The release of preloaded [3H]taurine from hippocampal slices from adult (3-month-old) and developing (7-day-old) mice was characterized under ischemic conditions in the presence of different NO-generating compounds, hydroxylamine, sodium nitroprusside, and S-nitroso-N-acetylpenicillamine (SNAP), using a superfusion system. The ischemia-induced taurine release at both ages was markedly enhanced by 1.0 mM nitroprusside and 1.0 mM SNAP, whereas 5.0 mM hydroxylamine was effective only in adults. The nitroprusside- and SNAP-induced releases were reduced by the inhibitors of NO synthase (nitroarginine and 7-nitroindazole) and NO-sensitive soluble guanylyl cyclase [1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one], suggesting involvement of the NO/cGMP pathway. The release in ischemia in the absence of Na+ was modified by NO compounds only in adults; the 0.1 mM N-methyl-D-aspartate stimulated taurine release at both ages. The enhanced release of taurine associated with NO production could be beneficial to brain tissue under cell-damaging conditions and corroborates the neuroprotective role of this amino acid, particularly in the immature brain. 相似文献
6.
Taranukhin AG Taranukhina EY Saransaari P Djatchkova IM Pelto-Huikko M Oja SS 《Amino acids》2008,34(1):169-174
Summary. Taurine is a sulphur-containing amino acid abundant in the nervous system. It protects cells from ischemia-induced apoptosis,
but the mechanism underlying this is not well established. The aim of our study was to explore the effects of taurine on two
main pathways of apoptosis induced by ischemia: receptor-mediated and mitochondrial cell death. Brain slices containing the
supraoptic (SON) and paraventricular (PVN) nuclei of the hypothalamus were incubated in vitro under control and simulated
ischemic (oxygen-glucose deprivation for 30 min) conditions in the absence and presence of 20 mM taurine. Brain slices were
harvested after the 180-min “postischemic” period and fixed in 4% paraformaldehyde. To estimate apoptosis, immunostaining
was done for caspase-8 and caspase-9 in paraffin-embedded sections. Immunoreactive caspase-8 and caspase-9 cells were observed
in SON and PVN in all experimental groups, but in the “ischemic” group the expression of caspase-8 and caspase-9 and the number
of immunoreactive cells was significantly increased in both hypothalamic nuclei. Addition of taurine (20 mM) to the incubation
medium induced a marked decrease in caspase-8 and caspase-9 immunoreactivity after ischemia in SON and PVN when compared with
the taurine-untreated “ischemic” group. Taurine reduces ischemia-induced caspase-8 and caspase-9 expression, the key inductors
of apoptosis in SON and PVN.
Authors’ address: Dr. Andrey Taranukhin, Tampere Brain Research Center, Medical School, University of Tampere, FI-33014 Finland 相似文献
7.
El Idrissi A 《Amino acids》2008,34(2):321-328
Summary. We have determined the role of mitochondria in the sequestration of calcium after stimulation of cerebellar granule cells
with glutamate. In addition we have evaluated the neuroprotective role of taurine in excitotoxic cell death. Mitochondrial
inhibitors were used to determine the calcium buffering capacity of mitochondria, as well as how taurine regulates the ability
of mitochondria to buffer intracellular calcium during glutamate depolarization and excitotoxicity. We report here that pre-treatment
of cerebellar granule cells with taurine (1 mM, 24 h) significantly counteracted glutamate excitotoxicity. The neuroprotective
role of taurine was mediated through regulation of cytoplasmic free calcium ([Ca2+]
i
), and intra-mitochondrial calcium homeostasis, as determined by fluo-3 and 45Ca2+-uptake. Furthermore, the overall mitochondrial function was increased in the presence of taurine, as assessed by rhodamine
accumulation into mitochondria and total cellular ATP levels. We specifically tested the hypothesis that taurine reduces glutamate
excitotoxicity through both the enhancement of mitochondrial function and the regulation of intracellular (cytoplasmic and
intra-mitochondrial) calcium homeostasis. The role of taurine in modulating mitochondrial calcium homeostasis could be of
particular importance under pathological conditions that are characterized by excessive calcium overloads. Taurine may serve
as an endogenous neuroprotective molecule against brain insults.
Authors’ address: Abdeslem El Idrissi, Biology Department and Center for Developmental Neuroscience, College of Staten Island/CUNY,
6S-134 Staten Island, NY 10314, U.S.A. 相似文献
8.
Summary. We have recently reported that the nitric oxide (NO) donor, sodium nitroprusside (SNP), induces seizures which are associated
with an increase in the basal release of aspartate and glutamate from rat hippocampus (Kaku et al., 1998). In order to determine
whether taurine release occurs with SNP-induced seizures, we examined the effects of NO-related compounds, i.e., the NO trapper,
diethyldithiocarbamate (DETC), the superoxide radical scavenger, dithiothreitol (DTT), the xanthine oxidase inhibitor, oxypurinol
and the guanylyl cyclase inhibitor, 1H-(1,2,4)oxadiazole(4,3-a)quinoxalin-1-one (ODQ), on SNP-induced seizures and in vivo taurine release from rat hippocampus using microdialysis. Perfusion with 0.5 mM SNP provoked seizures and significantly increased
taurine release, with the increase in release occurring primarily during reperfusion with artificial cerebrospinal fluid lacking
SNP. Perfusion with 5 mM DETC significantly abolished the SNP-induced seizures and reduced taurine release during and after
perfusion with the drugs. Perfusion with 1 mM DTT significantly reduced both the frequency of the SNP-induced seizures and
taurine release during and after perfusion with the drugs. Perfusion with 1 mM oxypurinol or 0.5 mM ODQ did not reduce the
frequency of the SNP-induced seizures, but tended to decrease taurine release during and after perfusion with the drugs. These
results demonstrate that SNP-induced seizures are triggered by an increase in both NO and peroxynitrite and are related to
an increase in taurine release from rat hippocampus.
Received January 25, 2000/Accepted January 31, 2000 相似文献
9.
Summary. Taurine has been reported to enhance cholesterol 7α-hydroxylase (CYP7A1) mRNA expression in animal models. However, no in vitro studies of this effect have been reported. The Hep G2 human hepatoma cell line has been recognized as a good model for studying
the regulation of human CYP7A1. This work characterizes the effects of taurine on CYP7A1 mRNA levels of Hep G2 cells in a
dose- and time-dependent manner. In the dose-dependent experiment, Hep G2 cells were treated with 0, 2, 10 or 20 mM taurine
in the presence or absence of cholesterol 0.2 mM for 48 h. In the time-dependent experiment, Hep G2 cells were treated with
0 or 20 mM taurine for 4, 24 and 48 h with and without cholesterol 0.2 mM. Our data revealed that taurine showed time- and
dose-response effects on CYP7A1 mRNA levels in Hep G2 cells. However, glycine – a structural analogue of taurine – did not
have an effect on CYP7A1 gene expression. These results show that, in agreement to previous studies on animal models, taurine
induces the mRNA levels of CYP7A1 in Hep G2 cells, which could enhance cholesterol conversion into bile acids. Also, Hep G2
cell line may be an appropriate model to study the effects of taurine on human cholesterol metabolism. 相似文献
10.
Guz G Oz E Lortlar N Ulusu NN Nurlu N Demirogullari B Omeroglu S Sert S Karasu C 《Amino acids》2007,32(3):405-411
Summary. Ischemia-reperfusion (I/R) injury is one of the most common causes of renal dysfunction. Taurine is an endogenous antioxidant
and a membrane-stabilizing, intracellular, free beta-amino acid. It has been demonstrated to have protective effects against
I/R injuries to tissues other than kidney. The aim of this study was to determine whether taurine has a beneficial role in
renal I/R injury. Forty Wistar-Albino rats were allocated into four groups as follows: sham, taurine, I/R, and I/R + taurine.
Taurine 7.5 mg/kg was given intra-peritoneally to rats in the groups taurine and I/R + taurine. Renal I/R was achieved by
occluding the renal arteries bilaterally for 40 min, followed by 6 h of reperfusion. Immediately thereafter, blood was drawn
and tissue samples were harvested to measure 1) serum levels of BUN and creatinine; 2) serum and/or tissue levels of malondialdehyde
(MDA), glutathione (GSH), glucose 6-phosphate dehydrogenase (G-6PD), 6-phosphogluconate dehydrogenase (6-PGD) and glutathione
reductase (GSH-red); 3) renal morphology; and 4) immunohistochemical staining for P-selectin. Taurine administration reduced
I/R-induced increases in serum BUN and creatinine, and serum and tissue MDA levels (p < 0.05). Additionally, taurine lessened
the reductions in serum and tissue glutathione levels secondary to I/R (p < 0.05). Taurine also attenuated histopathologic
evidence of renal injury, and reduced I/R-induced P-selectin immunoreactivity (p < 0.05). Overall, then, taurine administration
appears to reduce the injurious effects of I/R on kidney. 相似文献
11.
Summary Taurine is a neuromodulator and osmoregulator in the central nervous system, also protecting neural cells against excitotoxicity. The effects of the ionotropic glutamate receptor agonists N-methyl-D-aspartate (NMDA), kainate and 2-amino-3-hydroxy-5-methyl-4-imidazolepropionate (AMPA) on [3H]taurine release from hippocampal slices from 3-month-old and 7-day-old mice were studied in cell-damaging conditions. Neural cell injury was induced by superfusing the slices in hypoxic, hypoglycemic and ischemic conditions and by exposing them to metabolic poisons, free radicals and oxidative stress. The release of taurine was greatly enhanced in these conditions at both ages, except in oxidative stress. In normal conditions the three glutamate agonists potentiated taurine release in the immature hippocampus in a receptor-mediated manner, but kainate receptors did not participate in the regulation in the adults. The ability of the agonists to evoke taurine release varied in the cell-damaging conditions, but the glutamate-receptor-activated release was generally operating in the immature hippocampus. This glutamate-receptor-evoked massive release of taurine could have significant neuroprotective effects, particularly in the developing hippocampus, countering the harmful actions of the simultaneously liberated excitatory amino acids. 相似文献
12.
Characterization of N-methyl-D-aspartate-evoked taurine release in the developing and adult mouse hippocampus 总被引:2,自引:0,他引:2
Taurine is an inhibitory amino acid acting as an osmoregulator and neuroromodulator in the brain, with neuroprotective properties. The ionotropic glutamate receptor agonist N-methyl-D-aspartate (NMDA) greatly potentiates taurine release from brain preparations in both normal and ischemic conditions, the effect being particularly marked in the developing hippocampus. We now characterized the regulation of NMDA-stimulated taurine release from hippocampal slices from adult (3-month-old) and developing (7-day-old) mouse using a superfusion system. The NMDA-stimulated taurine release was receptor-mediated in both adult and developing mouse hippocampus. In adults, only NO-generating compounds, sodium nitroprusside, S-nitroso-N-acetylpenicillamine and hydroxylamine reduced the release, as did also NO synthase inhibitors, 7-nitroindazole and nitroarginine, indicating that the release is mediated by the NO/cGMP pathway. On the other hand, the regulation of the NMDA-evoked taurine release proved to be somewhat complex in the immature hippocampus. It was not affected by the NOergic compounds, but enhanced by the protein kinase C activator 4 beta-phorbol 12-myristate 13-acetate and adenosine receptor A(1) agonists, N(6)-cyclohexyladenosine and R(-)N(6)-(2-phenylisopropyl)adenosine in a receptor-mediated manner. The activation of both ionotropic 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors and metabotropic glutamate group I receptors also enhanced the evoked release. The NMDA-receptor-stimulated taurine release could be a part of the neuroprotective properties of taurine, being important particularly under cell-damaging conditions in the developing hippocampus and hence preventing excitotoxicity. 相似文献
13.
Summary. Taurine as well as tauret (retinyliden taurine) levels were measured in locust Locusta migratoria compound eyes. HPLC measurements revealed relatively low taurine levels (1.9 ± 0.16 mM) in dark-adapted eyes. Glutamate,
aspartate and glycine levels were 2.0 ± 0.2, 2.7 ± 0.4 and 3.0 ± 0.37 mM, respectively, while GABA was present only in trace
amounts. After about 4 h of light adaptation at 1500–2000 lx, amino acid levels in the compound eye were as follows: taurine,
1.8 ± 0.17 mM; glutamate, no change at 2.1 ± 0.2 mM; aspartate sharply increased to 4.7 ± 0.7 mM; glycine slightly decreased
to 2.8 ± 0.3 mM; and GABA trace levels. In the compound eye of locust Locusta migratoria, the existence of endogenous tauret in micro-molar range was established. In the dark, levels were several times higher compared
with compound eye after light adaptation 1500 lx for 3 h, as estimated by TLC in combination with spectral measurements. Existence
of tauret in compound eye is of special interest because in the compound eye, rhodopsin regeneration is based on photoregeneration. 相似文献
14.
Summary. Taurine and glutamate were monitored by microdialysis technique during various cerebral insults: a. Application of K+ triggered a cortical spreading depression (CSD). Taurine and glutamate increased concomitantly but recovery of glutamate
was faster than that of taurine. b. Application of NMDA induced also CSD but only taurine increased. c. Induction of an infarct
triggered repetitive CSDs. Taurine increased rapidly whereas glutamate rose slowly starting with some delay. d. After induction
of ischemia, taurine and glutamate increased after onset of depolarisation. The increase of glutamate occurred late after
a small, transient increase in parallel with the depolarisation. These data suggest a close functional relationship between
the changes of both amino acids. Therefore, they should be monitored together especially in clinical settings: during excitation,
only taurine will increase; during overexcitation, taurine will also increase but to a higher maximum followed by a moderate
rise of glutamate; after energy failure, taurine will accumulate to its highest level followed by a continuous rise of glutamate.
Received January 25, 2000/Accepted January 31, 2000 相似文献
15.
Summary. Recent literature suggests that both caffeine and taurine can induce diuresis and natriuresis in rat and man. Although they
act via different cellular mechanisms, their diuretic actions might be additive. This is of considerable interest, as several
commercially available energy drinks contain both substances.
In this study we examined the possible diuretic effects of caffeine and taurine in a cross-over-design in which 12 healthy
male volunteers received each of 4 different test drinks (750 ml of energy drink containing 240 mg caffeine and 3 g taurine,
the three other test drinks either lacked caffeine, taurine or both) after restraining from fluids for 12 h.
Mixed model analyses demonstrated that urinary output and natriuresis were significantly increased by caffeine (mean differences
243 ml and 27 mmol; both p < 0.001) and that there were no such effects of taurine (mean differences 59 ml and −4 mmol). Additionally, urinary osmolarity
at baseline was significantly related to the urinary output (p < 0.001). Urine osmolarity values at baseline and in the 6 h urine collection did not differ significantly between treatments.
Taken together, our study demonstrates that diuretic and natriuretic effects of the tested energy drink were largely mediated
by caffeine. Taurine played no significant role in the fluid balance in moderately dehydrated healthy young consumers. Consequently,
the diuretic potential of energy drinks will not differ significantly from other caffeine containing beverages. 相似文献
16.
Taurine has been thought to protect neural cells against cell-damaging conditions to which the hippocampus is particularly vulnerable. We studied now how the release of preloaded [3H]taurine is regulated by glutamate receptors in glucose-free media in slices prepared from the mouse hippocampus from developing (7 days old) and young adult (3 months old) mice, using a superfusion system. The lack of glucose enhanced taurine release more from slices from developing mice than from slices from adults. At both ages ionotropic glutamate agonists significantly increased the release in a receptor-mediated manner. Of the metabotropic glutamate receptors those belonging to the group III were effective. The release was enhanced in adult mice but attenuated in developing mice. Both effects were blocked by the receptor antagonists. The results show that glutamate receptors affect taurine release in the absence of glucose in which condition taurine should be neuroprotective. 相似文献
17.
The release of the inhibitory amino acid taurine is markedly enhanced under ischemic conditions in both adult and developing
brain stem, together with a pronounced increase in the release of the neuromodulator adenosine. We now studied the effects
of adenosine receptor agonists and antagonists on [3H]taurine release in the brain stem in normoxia and ischemia, using a superfusion system. Under standard conditions, the adenosine
A1 receptor agonist N6-cyclohexyladenosine (CHA) potentiated basal taurine release in adult mice, which response was blocked by the antagonist 8-cyclopentyl-1,3-dipropylxanthine
(DPCPX). CHA and the A2a receptor agonist 2-p-(2-carboxyethyl)phenylamino-5′-N-ethylcarboxaminoadenosinehydrochloride (CGS 21680) had no effect on the release in developing mice. In ischemia, CHA depressed
both basal and K+-stimulated taurine release in developing mice in a receptor-mediated manner, blocked by DPCPX. The A2a receptor agonist CGS 21680 was also inhibitory. Taurine and adenosine may thus not cooperate in developing mice to prevent
ischemic neuronal damage. On the other hand, CGS 21680 enhanced taurine release in the adult brain stem in ischemia, both
basal and K+-stimulated release being affected. These effects were abolished by the antagonist 3,7-dimethyl-1-propargylxanthine (DMPX),
indicating a receptor-mediated process. In this case elevated levels of taurine could be beneficial, protecting against hyperexcitation
and excitotoxicity. 相似文献
18.
The releases of endogenous glutamate, aspartate, GABA and taurine from hippocampal slices from 7-day-, 3-, 12-, and 18-month-old mice were investigated under cell-damaging conditions using a superfusion system. The slices were superfused under hypoxic conditions in the presence and absence of glucose and exposed to hydrogen peroxide. In the adult hippocampus under normal conditions the basal release of taurine was highest, with a response only about 2-fold to potassium stimulation (50 mM). The low basal releases of glutamate, aspartate, and GABA were markedly potentiated by K+ ions. In general, the release of the four amino acids was enhanced under all above cell-damaging conditions. In hypoxia and ischemia (i.e., hypoxia in the absence of glucose) the release of glutamate, aspartate and GABA increased relatively more than that of taurine, and membrane depolarization by K+ markedly potentiated the release processes. Taurine release was doubled in hypoxia and tripled in ischemia but K+ stimulation was abolished. In both the mature and immature hippocampus the release of glutamate and aspartate was greatly enhanced in the presence of H2O2, that of aspartate particularly in developing mice. In the immature hippocampus the increase in taurine release was 10-fold in hypoxia and 30-fold in ischemia, and potassium stimulation was partly preserved. The release processes of the four amino acids in ischemia were all partially Ca2+-dependent. High concentrations of excitatory amino acids released under cell-damaging conditions are neurotoxic and contribute to neuronal death during ischemia. The substantial amounts of the inhibitory amino acids GABA and taurine released simultaneously may constitute an important protective mechanism against excitatory amino acids in excess, counteracting their harmful effects. In the immature hippocampus in particular, the massive release of taurine under cell-damaging conditions may have a significant function in protecting neural cells and aiding in preserving their viability. 相似文献
19.
Mühling J Burchert D Langefeld TW Matejec R Harbach H Engel J Wolff M Welters ID Fuchs M Menges T Krüll M Hempelmann G 《Amino acids》2007,33(3):511-524
Summary. We examined the effects of DON [glutamine-analogue and inhibitor of glutamine-requiring enzymes], alanyl-glutamine (regarding
its role in neutrophil immunonutrition) and alanyl-glutamine combined with L-NAME, SNAP, DON, β-alanine and DFMO on neutrophil
amino and α-keto acid concentrations or important neutrophil immune functions in order to establish whether an inhibitor of
•NO-synthase [L-NAME], an •NO donor [SNAP], an analogue of taurine and a taurine transport antagonist [β-alanine], an inhibitor
of ornithine-decarboxylase [DFMO] as well as DON could influence any of the alanyl-glutamine-induced effects. In summary,
irrespective of which pharmacological, metabolism-inhibiting or receptor-mediated mechanisms were involved, our results showed
that impairment of granulocytic glutamine uptake, modulation of intracellular glutamine metabolisation and/or de novo synthesis
as well as a blockade of important glutamine-dependent metabolic processes may led to significant modifications of physiological
and immunological functions of the affected cells. 相似文献
20.
Taurine release modified by GABAergic agents in hippocampal slices from adult and developing mice 总被引:2,自引:0,他引:2
Summary. In order to characterize the possible regulation of taurine release by GABAergic terminals, the effects of several agonists
and antagonists of GABA receptors on the basal and K+-stimulated release of [3H]taurine were investigated in hippocampal slices from adult (3-month-old) and developing (7-day-old) mice using a superfusion
system. Taurine release was concentration-dependently potentiated by GABA, which effect was reduced by phaclofen, saclofen
and (1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid (TPMPA) at both ages, suggesting regulation by both GABAB and GABAC receptors. The involvement of GABAA receptors could not be excluded since the antagonist bicuculline was able to affect both basal and K+-evoked taurine release. Furthermore, several GABAB receptor effectors were able to inhibit K+-stimulated taurine release in the adults, while the GABAC receptor agonists trans-4-aminocrotonic acid (TACA) and cis-4-aminocrotonic acid (CACA) potentiated this release. The potentiation
of taurine release by agents acting on the three types of GABA receptors in both adult and developing hippocampus further
indicates the involvement of transporters operating in an outward direction. This inference is corroborated by the moderate
but significant inhibition of taurine uptake by the same compounds.
Received June 28, 1999, Accepted August 31, 1999 相似文献