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1.
Summary. The main objective of the present study was to evaluate the in vivo and in vitro effect of Arg on serum nucleotide hydrolysis. The action of Nω-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase, on the effects produced by Arg was also examined.
Sixty-day-old rats were treated with a single or a triple (with an interval of 1 h between each injection) intraperitoneal
injection of saline (group I), Arg (0.8 g/kg) (group II), L-NAME (2.0 mg/kg or 20 mg/kg) (group III) or Arg (0.8 g/kg) plus
L-NAME (2.0 mg/kg or 20 mg/kg) (group IV) and were killed 1 h later. The present results show that a triple Arg administration
decreased ATP, ADP and AMP hydrolysis. Simultaneous injection of L-NAME (20 mg/kg) prevented such effects. Arg in vitro did not alter nucleotide hydrolysis. It is suggested that in vivo Arg administration reduces nucleotide hydrolysis in rat serum, probably through nitric oxide or/and peroxynitrite formation.
Both are first authors. 相似文献
2.
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
3.
Garcia RF Gazola VA Barrena HC Hartmann EM Berti J Toyama MH Boschero AC Carneiro EM Manso FC Bazotte RB 《Amino acids》2007,33(1):151-155
Summary. Our purpose was to determine the blood amino acid concentration during insulin induced hypoglycemia (IIH) and examine if the
administration of alanine or glutamine could help glycemia recovery in fasted rats. IIH was obtained by an intraperitoneal
injection of regular insulin (1.0 U/kg). The blood levels of the majority of amino acids, including alanine and glutamine
were decreased (P < 0.05) during IIH and this change correlates well with the duration than the intensity of hypoglycemia. On the other hand,
the oral and intraperitoneal administration of alanine (100 mg/kg) or glutamine (100 mg/kg) accelerates glucose recovery.
This effect was partly at least consequence of the increased capacity of the livers from IIH group to produce glucose from
alanine and glutamine. It was concluded that the blood amino acids availability during IIH, particularly alanine and glutamine,
play a pivotal role in recovery from hypoglycemia. 相似文献
4.
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
5.
Summary. Antiakinsic effects of the uncompetitive NMDA antagonists, memantine, amantadine and MK-801, and competitive antagonists,
CGP 40116, alone or in co-administration with acute subthreshold dose of L-Dopa (5 mg/kg) in MPTP-treated mice, functional
alterations induced by acute MK-801 in combinations with neuroleptic compounds or behavioural deficits following postnatal
administration of MK-801 were investigated. Memantine and amantadine injected 60 min before the subthreshold dose of L-Dopa
(5 mg/kg), induced antiakinesic actions in hypokinesic MPTP-treated mice. Concurrently, higher doses of memantine and MK-801
caused dyskinesic changes, reducing further rearing (10 and 30 mg/kg) and locomotor (30 mg/kg) behaviour of the MPTP mice;
MK-801 elevated locomotion (0.1 mg/kg) but reduced rearing (0.3 mg/kg). In control, saline-treated mice, memantine (3, 10
and 30 mg/kg) and MK-801 (0.1 and 0.3 mg/kg) increased locomotor behaviour but decreased rearing behaviour. In rats, MK-801
induced marked increases in locomotor activity and disruptions of circular swim maze acquisition that were to greater or lesser
extents blocked or potentiated by neuroleptic compounds: SCH 23390 (0.005 and 0.05 mg/kg) and clozapine (5.0 and 10.0 mg/kg)
dose-dependently antagonised MK-801 (0.3 mg/kg) induced locomotor activity whereas raclopride (0.1 mg/kg) and haloperidol
(0.1 mg/kg) attenuated it dose-specifically. Amperozide (0.5 mg/kg) attenuated the MK-801 effect but potentiated it at the
2.0 mg/kg dose. In the circular swim maze, raclopride (0.01 mg/kg) and SCH 23390 (0.05 mg/kg) improved the acquisitive performance
of rats administered MK-801 (0.03 mg/kg) acutely whereas clozapine (10.0 mg/kg) and amperozide (2.0 mg/kg) deteriorated the
performance of MK-801-treated rats. Postnatal administration of MK-801 (0.05 mg/kg, day 11 after birth) induced severe functional
alterations in adult mice. At 70 days of age, MK-801 mice showed an initial hypoactivity followed by marked hyperactivity
in the motor activity test chambers. These mice showed deficits in habituation, a nonassociative form of learning. Their hyperactivity
in the test chambers was reversed by a low dose of d-amphetamine (0.25 mg/kg). Taken together, these findings display a wide
range of acute/long-term functional alterations induced by NMDA antagonists, particularly MK-801, associated with animal models
of brain disorders.
Received July 9, 2001 Accepted August 6, 2001 Published online June 17, 2002 相似文献
6.
Summary. The aim of this study was to evaluate the effect of endotoxin on PMN leukocyte respiratory burst activity by measuring G6PD,
NADPH oxidase and XO activities in guinea pig. In addition, the possible protective role of taurine against endotoxin-mediated
PMN leukocyte function was examined. All experiments were performed with four groups (control, taurine, endotoxemia, taurine
plus endotoxin) of ten guinea pigs. After the endotoxin was administrated (4 mg/kg) both G6PD and NADPH oxidase activities
were significantly reduced compared with the control group. NADPH oxidase activity returned to the control value and G6PD
activity also increased but it did not reach the control value. However when taurine was administrated (300 mg/kg) the activity
of NADPH oxidase reached the control value; furthermore, G6PD activity also increased but it could not reach to the control
value. When taurine was administrated alone, no effect on these enzymes was observed. Following the endotoxin administration,
the activity of XO considerably increased. When taurine was administrated together with endotoxine and alone, this activity
decreased compared to control value in both conditions. These results indicate that the O2
•− formation in PMN leukocytes after the endotoxin administration is ensured by the catalysis of XO due to the inhibited NADPH
oxidase activity. It was observed that taurine has considerable anti-inflammatory and antioxidant effects. However, conflicting
results were obtained when taurine was administrated alone or together with an oxidant agent. 相似文献
7.
Sved DW Godsey JL Ledyard SL Mahoney AP Stetson PL Ho S Myers NR Resnis P Renwick AG 《Amino acids》2007,32(4):459-466
Summary. Three biodisposition studies with taurine were performed in male and female adult rats at dosages of 30 and 300 mg/kg. A single
oral dose of 14C-taurine was rapidly absorbed, distributed to tissues and excreted unchanged in urine. Elimination of radioactivity from
intracellular pools was slow. Pre-treatment of animals for 14 days with unlabelled taurine did not significantly affect the
fate of 14C-taurine. At the higher dose there was more extensive excretion combined with a lower percentage of the dose in the carcass,
indicating the possibility of saturation of the tubular reabsorption mechanism for taurine. Daily administration of unlabelled
taurine for 14 days did not result in an increase in total taurine in the brain. The data indicate that exogenous taurine
rapidly equilibrates with endogenous body pools and that any excess is rapidly eliminated by the kidneys. 相似文献
8.
Summary. The aim of the present study was to measure MPO activity in PMN leukocytes after endotoxin administration, and to compare
the levels of NO2
− competing with taurine for reaction with HOCl. Furthermore we aimed to determine TauCl levels, a product of MPO–H2O2–Halide system, and to evaluate anti-inflammatory properties of PMN in endotoxemia. In addition, our second objective was
to investigate the effect of taurine, an antioxidant amino acid, on anti-bactericidal and anti-inflammatory functions of PMN
after administration of endotoxin together with taurine.
All experiments were performed with four groups (control, taurine, endotoxemia, and taurine plus endotoxin) of ten guinea
pigs. After endotoxin administration (4 mg/kg), MPO activities increased and taurine levels decreased. Therefore levels of
TauCl, NO2
•− increased. We observed the effects of taurine as conflicting. When taurine was administrated alone (300 mg/kg), all of these
parameters decreased.
Consequently, we suggested that taurine is influential in infected subjects but not on healthy ones as an antioxidative amino
acid. In addition, we believe that in vivo effects of taurine may differ from those in vitro depending on its dosage. 相似文献
9.
Summary. We have investigated the idea that nicotinamide, a non-selective inhibitor of the sentinel enzyme Poly(ADP-ribose) polymerase-I
(PARP-1), provides neuroprotection against the long-term neurological changes induced by perinatal asphyxia. Perinatal asphyxia
was induced in vivo by immersing foetuses-containing uterine horns removed from ready-to-deliver rats into a water bath for
20 min. Sibling caesarean-delivered pups were used as controls. The effect of perinatal asphyxia on neurocircuitry development
was studied in vitro with organotypic cultures from substantia nigra, neostriatum and neocortex, platted on a coverslip 3
days after birth. After approximately one month in vitro (DIV 25), the cultures were treated for immunocytochemistry to characterise neuronal phenotype with markers against the N-methyl-D-aspartate
receptor subunit 1 (NR1), the dopamine pacemaker enzyme tyrosine hydroxylase (TH), and nitric oxide synthase (NOS), the enzyme
regulating the bioavailability of NO. Nicotinamide (0.8 mmol/kg, i.p.) or saline was administered to asphyctic and caesarean-delivered
pups 24, 48 and 72 h after birth.
It was found that nicotinamide treatment prevented the effect of perinatal asphyxia on several neuronal parameters, including
TH- and NOS-positive neurite atrophy and NOS-positive neuronal loss; supporting the idea that nicotinamide constitutes a therapeutic
alternative for the effects produced by sustained energy-failure conditions, as occurring during perinatal asphyxia. 相似文献
10.
Summary. So-called energy drinks with very high amounts of taurine (up to 4000 mg/l are usually granted by certificates of exemption)
are increasingly offered on the market. To control the currently valid maximum limits of taurine in energy drinks, a simple
and rapid analytical method is required to use it routinely in food monitoring. In this article, we describe a fast and efficient
analytical method (FTIR-spectroscopy) that is able to reliably characterize and quantify taurine in energy drinks. The determination
of taurine in energy drinks by FTIR was compared with amino acid analyzer (ion chromatography with ninhydrin-postcolumn derivatization).
During analysis of 80 energy drinks, a median concentration of 3180 mg/l was found in alcohol-free products, 314 mg/l in energy
drinks with spirits, 151 mg/l in beer-containing drinks and 305 mg/l in beverages with wine. Risk analysis of these products
is difficult due to the lack of valid toxicological information about taurine and its interferences with other ingredients
of energy drinks (for example caffeine and alcohol). So far, the high taurine concentrations of energy drinks in comparison
to the rest of the diet are scientifically doubtful, as the advertised physiological effects and the value of supplemented
taurine are unproven. 相似文献
11.
Summary. The purpose of this study was to determine whether the γ-aminobutyric acid (GABA) affects the rate of brain protein synthesis
in male rats. Two experiments were done on five or three groups of young rats (5 wk) given the diets containing 20% casein
administrated 0 mg, 25 mg, 50 mg, 100 mg or 200 mg/100 g body weight GABA dissolved in saline by oral gavage for 1 day (d)
(Experiment 1), and given the diets contained 0%, 0.25% or 0.5% GABA added to the 20% casein diet (Experiment 2) for 10 d.
The plasma concentration of growth hormone (GH) was the highest in rats administrated 50 mg and 100 mg/100 g body weight GABA.
The concentration of serum GABA increased significantly with the supplementation groups. The fractional (Ks) rates of protein
synthesis in brain regions, liver and gastrocnemius muscle increased significantly with the 20% casein + 0.25% GABA diet and
still more 20% casein + 0.5% GABA compared with the 20% casein diet. In brain regions, liver and gastrocnemius muscle, the
RNA activity [g protein synthesized/(g RNA·d)] significantly correlated with the fractional rate of protein synthesis. The
RNA concentration (mg RNA/g protein) was not related to the fractional rate of protein synthesis in any organ. Our results
suggest that the treatment of GABA to young male rats are likely to increase the concentrations of plasma GH and the rate
of protein synthesis in the brain, and that RNA activity is at least partly related to the fractional rate of brain protein
synthesis. 相似文献
12.
Summary. 3-Hydroxynorvaline (HNV; 2-amino-3-hydroxypentanoic acid), a microbial L-threonine analogue, is toxic to mammalian cells and
displays antiviral properties. In view of this, we investigated the toxicity and/or potential teratogenicity of HNV in developing
chicken and mouse embryos. HNV was administered to chicken embryos (in ovo; dose 75–300 μmole/egg; 48 h post-incubation) and pregnant Hanover NMRI mice (per os; total dose 900–1800 mg/kg body mass; gestation days 7–9). Control animals received sterile saline solutions. Harvested embryos
(chicken embryos, 10 days post-incubation; mouse embryos; gestation day 18) were fixed in glutaraldehyde and stereomicroscopically
inspected for signs of dysmorphogenesis. Body mass, body and toe length and mortality of chicken embryos, and the body mass
and mortality of mouse embryos were recorded. HNV exposure significantly increased the incidence of embryotoxic (growth retardation,
toxic mortality) and congenital defects in both chicken and mouse embryos. All the observed effects were dose-dependent. In
conclusion, HNV is an embryotoxic and teratogenic compound, which caused significant developmental delay and congenital defects
in developing chicken and mouse embryos. 相似文献
13.
Summary. Icilin, the peripheral cold channel agonist, activates TRPM8 and TRPA1, localized on dorsal root ganglia and trigeminal neurons
in rats. Icilin precipitates immediate wet-dog shakes in this species, which are antagonized by centrally acting mu and kappa
opioid agonists, implicating the central nervous system in the behavioral response. We studied the effect icilin has on glutamate
levels in the dorsal striatum, a brain region involved in movement. Icilin (0.25, 0.5 and 0.75 mg/kg, i.p.) elicited a dose-
and time-dependent increase in glutamate within the striatum, indicative of icilin’s neurochemical effect in rats. 相似文献
14.
Summary. Goldfish retinal explant outgrowth in the presence of fetal calf serum is stimulated by taurine. In the absence of it, but
with glucose in the medium, length of neurites is still elevated by the amino acid. Using the medium in the presence of glucose,
but in the absence of fetal calf serum, we explored the effect of optic tectum medium from cultures of them coming from goldfish
without crush of the optic nerve or 3, 5, 10, 14 and 20 days after crush. Retinal explants, intact or from goldfish with crush
of the optic nerve 10 days prior to starting the culture, were employed in order to measure the possible effect of optic tectum
media and the inter action with taurine. In other type of experiments the optic nerve was crushed 1, 2, 4, 7 and 10 days before
dissection of the optic tectum, and then co-cultured with intact or 10 days post-crush retinal explants. Optic tectum media
produced a time-dependent effect on outgrowth in lesioned retinas with a maximum effect around 5 days after the lesion for
the corresponding optic tectum. Taurine, 4 mM, did not further affect the outgrowth in the presence of optic tectum media,
but did significantly increase length of neurites either in intact or in post-lesion retinas. Co-culture of optic tectum at
different days post-lesion and retinas at 10 days post-lesion increased the outgrowth around 4 days post-lesion, in a preparation
resulting in mutual effects of both types of tissues. The addition of taurine in these conditions did not further increase
outgrowth, rather inhibited it according to the time after lesion of optic nerve corresponding to the co-cultured optic tectum.
The effect of taurine was concentration-dependent, since 0.2 mM was more effective than 2 or 4 mM in the presence of optic
tectum with lesion of 2 days. These results demonstrate the time-course of the regeneration processes in the visual system
of goldfish, indicating the crucial periods after crush in which the tectum could produce stimulation and later decrease or
no effect on outgrowth from the retina. In addition, they are evidences of the interaction between taurine and optic tectum
production of time-produced specific agents. The mechanisms underlying these effects are closely related to calcium, as it
was demonstrated by the addition of extracellular or intracellular chelators to the medium, which inhibited the effects of
the optic tectum and the trophic properties of taurine in this system. The inhibitor of taurine transport, guanidoethylsulfonate,
also decreased the stimulatory effects of the optic tectum and of taurine, indicating an interaction of substances produced
by the tectum with taurine, and an effect of taurine mediated through its entrance to the cells. Overall, retinal explants
outgrowth in the absence of fetal calf serum, the interaction of agents of the optic tectum and taurine modulates outgrowth
from the retina, and these effects are mediated by calcium levels and by the levels of intracellular taurine. 相似文献
15.
Summary. We previously reported that L-leucine suppresses myofibrillar proteolysis in chick skeletal muscles. In the current study,
we compared the effects of L- and D-enantiomers of leucine on myofibrillar proteolysis in skeletal muscle of chicks. We also
assessed whether leucine itself or its metabolite, α-ketoisocaproate (α-KIC), mediates the effects of leucine. Food-deprived
(24 h) chicks were orally administered 225 mg/100 g body weight L-leucine, D-leucine or α-KIC and were sacrificed after 2 h.
L-Leucine administration had an obvious inhibitory effect on myofibrillar proteolysis (plasma Nτ-methylhistidine concentration) in chicks while D-leucine and α-KIC were much more effective. We also examined the expression
of the proteolytic-related genes (ubiquitin, proteasome, m-calpain and cathepsin B) by real-time PCR of cDNA in chick skeletal
muscles. Ubiquitin mRNA expression was decreased by D-leucine and α-KIC but not L-leucine. Proteasome and m-calpain mRNA expressions
as well as cathepsin B mRNA expression were likewise decreased by L-leucine, D-leucine and α-KIC. These results indicate that
D-leucine and α-KIC suppress proteolytic-related genes, resulting in an decrease in myofibrillar proteolysis while L-leucine
is much less effective in skeletal muscle of chicks, may be explain by conversion of D-leucine to α-KIC. 相似文献
16.
Summary. L-Tryptophan (TRP) is the precursor amino acid for the synthesis of serotonin (5-HT). 5-HT is effective both on the food intake
and gastrointestinal system contractility. The aim of this study was to search the effects of systemic TRP treatment on 5-HT
levels of ileum and searching the effect of ileal contractility and oxidant status. Swiss-albino mice were divided into two
groups: 1. Control, 2. TRP-treated (100 mg/kg/24 h, i.p., for 7 days). Body weights were recorded at the beginning and at
the end of experiments. Acetylcholine-induced contractile responses in the isolated ileum were recorded on polygraph. Ileal
tissue malondialdehyde and glutathione levels determined by spectrophotometric and ileal tissue 5-HT levels were measured
by immunohistochemical methods. TRP treatment decreased body weight and increased ileal contractile response. In the TRP-treated
group, ileum malondialdehyde levels increased and glutathione levels decreased. Immunohistochemical detection showed that
ileal 5-HT levels were increased by TRP treatment. There is a relationship between increased oxidative stress and increased
contractility in the ileal tissue of the TRP-treated animals. These effects may be related to increased ileal 5-HT synthesis. 相似文献
17.
In our study, the short-term effects of caffeine on L- arginine metabolism in the brains of rats were investigated. Caffeine
was given orally at two different doses: 30 mg/kg and 100 mg/kg (a high non-toxic dose). Brain tissue arginase activity in
rats from the caffeine-treated groups decreased significantly compared with the control group. Malondialdehyde (MDA) levels
in the brain tissue and serum of animals in the caffeine groups also decreased significantly. Brain tissue and serum nitric
oxide (NO) levels increased significantly after caffeine administration. Tumor necrosis factor-α (TNF-α) levels were also
investigated in rat serum, but there was no statistically significant difference between the TNF-α levels of the caffeine-treated
rats groups and the control rats. Our study indicates that brain arginase activity decreases after caffeine administration
at doses of 30 mg/kg and 100 mg/kg. As a result, we can say that arginine induces production of NO in the organism. 相似文献
18.
S. Canpolat N. Tug A. D. Seyran S. Kumru B. Yilmaz 《Journal of physiology and biochemistry》2010,66(1):23-28
This study was designed to investigate effects of raloxifene (RLX) and estradiol on bone formation and resorption in intact
and ovariectomized (ovx) rat models. In the intact model, a total of 24 adult female rats were divided into three groups:
Controls subcutaneously received saline alone. RLX (2 mg/kg) and estradiol (30 μg/kg) were injected to two groups of animals
for a period of 6 weeks at two daily intervals. In the second model, rats (n = 24) were ovx and allowed to recover for a period of at least 3 weeks. Control group received vehicle alone. Remaining rats
were divided into two groups and injected with RLX (2 mg/kg) and estradiol (30 μg/kg) for 6 weeks. Urine samples were collected
from all animals 24 h after the last drug administration. Urinary deoxypyridinoline (DPD) was measured by ELISA. Serum parathyroid
hormone (PTH), calcitonin, and osteocalcin levels were measured by immunoradiometric method. Serum concentrations of alkaline
phosphatase (ALP), Ca, and inorganic phosphate were determined by enzymatic–colorimetric method. Lumbar vertebrae (L2) of
all animals were dissected out and processed for histopathological evaluation. Removal of ovaries significantly elevated urinary
DPD levels (p < 0.01) compared with intact controls. Treatment of both intact and ovx rats with estradiol resulted in significant decreases
(p < 0.01) in DPD values. RLX administration had no significant effect in the intact rats, but it remarkably reduced bone turnover
in the ovx animals (p < 0.001). Both estradiol and RLX produced conflicting effects on serum ALP, osteocalcin, and PTH levels in both animal models.
These findings suggest that RLX exerts its protective effects by reducing bone resorption, similar to that of estradiol, in
ovx rats. 相似文献
19.
Previous behavioral studies on triazolam (TZ), which are small in number, could only speculate about tolerance to the anxiolytic effect of TZ, as the experiments did not cover sufficient time (of 4 to 7 days) for tolerance to develop. Therefore longer time for chronic TZ administration is used. We investigated the effects of TZ on motor activity and exploratory behavior using plus maze and open field. Three experiments were conducted. In the first, five groups of rats were acutely treated with different doses of TZ (0.25 mg/kg-4.0 mg/kg). In the second set of experiments, rats were treated chronically with a single daily dose of TZ (started with 0.25 mg/kg and increased by time to 1.0 mg/kg) for 5 weeks (representing clinical use). In the third, rats were treated chronically with three daily doses of TZ (started with 0.25 mg/kg and increased by time to 0.5 mg/kg) for 20 days (mimicking drug abuse). Acute TZ administration produced dose dependent anxiolytic effects and a decrease in motor activity with higher doses. Chronically treated rats, either once daily or three times daily doses, showed tolerance to both anxiolytic and sedative effects of TZ. It may be concluded that tolerance to the anxiolytic and sedative effects of TZ would develop after chronic administration either with clinical use or its abuse. 相似文献
20.
The role of striatal metabotropic glutamate receptors in degeneration of dopamine neurons: review article 总被引:1,自引:0,他引:1
Summary. Degeneration of dopaminergic nigrostriatal neurons is a primary cause of Parkinson's disease. Oxidative stress, excitotoxicity
and mitochondrial failure are thought to be key mechanisms resposible for degeneration of dopaminergic cells. We found that
the selective antagonist of the mGluR5 subtype MPEP in a dose of 5 mg/kg diminshed basal and veratridine (100 μM)-stimulated dopamine release in rat striatum in an in vivo model of microdialysis. In contrast, MPEP given intrastriatally in a high concentration (500 μM) enhanced the striatal extracellular concentration of dopamine. DCG-IV (100 μM), a non-selective agonist of group II mGluRs, inhibited the veratridine-stimulated striatal dopamine release. In an animal
model of neuroxicity in vivo, methamphetamine (5 × 10 mg/kg, injected at 2 h intervals) produced deficits in the striatal content of dopamine and its
metabolites DOPAC and HVA 72 h after the treatment. MPEP (5 × 5 mg/kg) given before each methamphetamine injection reversed
the decrease in the striatal content of dopamine and diminished the methamphetamine-induced dopamine outflow from nigrostriatal
terminals. It is concluded that the MPEP-produced blockade of mGluR5 situated on dopaminergic cells, or the suppression of
glutamate release in the subthalamic nucleus or substantia nigra pars reticulata may directly and indirectly cause a decrease
in striatal dopamine release. However, inhibitory effect of DCG-IV on dopamine release can be induced by attenuation of excitatory
input from corticostriatal terminals by activation of mGluR2/3. Regulation of dopamine carriers by MPEP, an antagonist of
group I mGluRs may be responsible for the reversal of toxicity induced by methamphetamine.
Received July 7, 2001 Accepted August 6, 2001 Published online September 10, 2002 相似文献