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1.
The neuronal NOS inhibitor
Rat striata were exposed to 15 mM quinolinic acid (QUIN), or QUIN plus the nitric oxide synthase inhibitors S-methyl-
-thiocitrulline dihydrochloride (
-MIN) or 7-nitroindazole monosodium salt (7-NINA) for 21 days. Co-administration of 100 μM or 1 mM
-MIN with QUIN significantly reduced lesion volume compared to QUIN alone. Co-administration of 1 μM or 10 μM
-MIN with QUIN had no significant effect. There was no significant effect of 7-NINA co-administered with QUIN compared to QUIN alone.
-MIN reduction of lesion volume supports the contention that neuronal nitric oxide synthase is a mediator of excitotoxic injury. 相似文献
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2.
The effects of
The present study examined the effects of GM1 ganglioside and the monoamine oxidase B (MAO-B) inhibitor
-deprenyl, alone and in combination, on striatal dopamine (DA) and DOPAC levels, and the density of tyrosine hydroxylase (TH) positive neurons in the substantia nigra pars compacta (SNc) of C57bl/6J mice following MPTP administration (20 mg/kg, s.c., twice daily for 5 days). GM1 treatment (30 mg/kg, i.p., daily for 3 weeks, beginning 24 h after the last MPTP injection) partially restored striatal DA levels and rescued SNc neurons. A high dose of
-deprenyl, inhibiting MAO-B activity, (10 mg/kg, i.p. every other day for 3 weeks beginning 3 days after the last MPTP injection) increased striatal DA content, but did not rescue TH-positive SNc neurons. A low dose of
-deprenyl (0.01 mg/kg, i.p. every other day for 3 weeks beginning 3 days after the last MPTP injection) had no effect on either striatal neurochemistry or the rescue of SNc TH-positive neurons. Co-administration of GM1 and high dose
-deprenyl caused a synergistic increase in striatal DA levels, above that obtained with either GM1 or high dose
-deprenyl alone. Co-administration of GM1 and low dose
-deprenyl was not only not synergistic, but caused GM1s effects to be antagonized. The results do not confirm previous findings that low dose
-deprenyl administration in vivo after MPTP can rescue SNc neurons. Given GM1's potential as an adjunct to present anti-parkinsonian medications which include
-deprenyl, it will be important to further investigate the interactions between these two potential therapies. 相似文献
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3.
p-Chlorophenylalanine and fluoxetine inhibit
-Fenfluramine, a putative serotonin releaser and reuptake inhibitor, is commonly prescribed for the treatment of obesity. Brain sites activated by
-fenfluramine have been mapped via the expression of the immediate early gene Fos. However, it is not clear that serotonin release in the brain mediates the effects of
-fenfluramine on Fos expression. The present study determined whether
-fenfluramine induces the expression of Fos in the brain through the release of serotonin. Rats were pretreated either with the serotonin depleting drug p-chlorophenylalanine (PCPA) or with the serotonin reuptake inhibitor fluoxetine. Both drugs inhibited
-fenfluramine-induced Fos expression in the cingulate cortex, frontal cortex, and the parvocellular subdivision of the paraventricular nucleus of the hypothalamus. Neither drug reduced
-fenfluramine-induced Fos responses in several other brain areas, including the caudate–putamen, amygdala, and brainstem regions such as the lateral parabrachial nucleus and nucleus of the solitary tract. These results indicate regional specificity of mechanisms mediating
-fenfluramine-induced Fos expression. It is likely that
-fenfluramine-induced Fos expression at various sites in the brain is mediated via a combination of serotonin release and other, as yet unidentified, neurotransmitters. 相似文献
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4.
Modulatory effect of
We investigated whether NG-nitro-
-arginine methyl ester (
-NAME), a specific inhibitor of nitric oxide synthase (NOS), can modify the stress-induced adrenocorticotropic hormone (ACTH) and corticosterone responses, because we found that immobilization-induced stress increases NOS mRNA and protein levels and enzyme activity in the adrenal cortex. The physiological significance of these phenomena, however, remains unknown. Plasma ACTH and corticosterone levels were determined by radioimmunoassay (RIA) of systemic blood samples and NOS enzyme activity was measured as the rate of [3H]arginine conversion to [3H]citrulline in the presence of tissue homogenate of adrenal cortex separated from the adrenal gland. The NOS enzyme activity in the adrenal cortex of rats pre-injected with saline at 2 h after the 2-h immobilization was significantly higher (P<0.01) than that in the non-stressed controls. Pre-injection of
-NAME (100 mg/kg, s.c.) almost completely abolished the activity. This dose of
-NAME maintained a significantly elevated plasma corticosterone level (P<0.05, compared with basal level) even 2 h after the 2-h stress, whereas the plasma corticosterone level in rats pre-injected with saline returned to the basal level at the same time point. Plasma ACTH level in
-NAME-pre-treated rats was higher than that in those pre-treated with saline 2 h after the stress, but the difference was not significant. This dose of
-NAME did not influence plasma ACTH or corticosterone levels under resting conditions without stress. These findings suggest that the stress-induced increase in NO synthesis in the adrenal cortex can modify the stress-induced corticosterone response to facilitate the recovery from the elevated corticosterone secretion by stress in the adrenal cortex to the resting basal level. 相似文献
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5.
Characterization of [
Coated vesicles prepared from bovine brain cerebral cortex exhibited [
]5-hydroxytryptamine (5-HT, serotonin) and [
]spiperone binding activities. The binding activities were localized in the inner core vesicles. Binding reached an equilibrium level by 30–45 min at 30°C, and was reversed by the addition of 100 μM 5-HT for [
]5-HT binding or 10 μM ketanserin for [
]spiperone binding. The saturation binding experiments indicated a single class of binding sites for [
]5-HT and [
]spiperone with apparent Kd values of 2.4 and 1.75 nM, respectively. The binding of [
]5-HT was displaced by 5-HT and 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), but not by ketanserin. The binding of [
]spiperone was displaced by spiperone and ketanserin but not by 5-HT or 8-OH-DPAT even at 1 mM. The coated vesicles were shown by immunoblotting assay to contain α-subunits of GTP-binding proteins, Gαs, Gαi2, Gαi3, Gαo and Gαq/11. Forskolin-stimulated adenylate cyclase activity in the coated vesicles was inhibited to 80% of the control level by 5-HT or 8-OH-DPAT. These results suggested that 5-HT1A and 5-HT2A receptors are present in bovine brain coated vesicles and that the 5-HT1A receptors are coupled to adenylate cyclase activity via GTP binding proteins. 相似文献
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6.
Activation of protein kinase C by phorbol dibutyrate potentiates [
Effects of activation of protein kinase C (PKC) on N-methyl-
-aspartate (NMDA) receptor function were analyzed by quantitative autoradiography using [
]MK-801 in rat brain slices. The density of [
]MK-801 binding was highest in hippocampus and high levels were found in cortex, striatum and thalamus. Levels in brainstem and molecular layer of cerebellum were low. The receptor binding was markedly decreased in almost all areas by addition of 2.5 mM Mg2+. After activation of PKC by 100 nM phorbol-12,13-dibutyrate (PDBu), [
]MK-801 binding was increased in most areas, but binding levels were not changed in brainstem and cerebellum. The elevated [
]MK-801 binding produced by PDBu was significantly inhibited by addition of Mg2+ except in inferior colliculus and cerebellum. These results suggest that activation of PKC potentiates NMDA receptor function in a region-specific manner in the rat brain. 相似文献
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7.
Monoamine oxidase-dependent metabolism of dopamine in the striatum and substantia nigra of
Donato A. Di Monte Louis E. DeLanney Ian Irwin Joyce E. Royland Piu Chan Michael W. Jakowec J. William Langston 《Brain research》1996,738(1)
The effects of monoamine oxidase (MAO) inhibitors on the metabolism of dopamine synthesized from exogenous
-DOPA were investigated in the striatum and substantia nigra of squirrel monkeys. Administration of a single dose of
-DOPA (methyl ester, 40 mg/kg, i.p.) caused a significant increase in the levels of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) and in the DOPAC/dopamine ratio in the putamen, caudate and substantia nigra. These changes were more pronounced in the substantia nigra than in the striatum and within the striatum of
-DOPA-treated monkeys, levels of dopamine and its metabolites were higher in the putamen than in the caudate nucleus. When
-DOPA treatment was preceded by the injection of clorgyline or deprenyl at a concentration (1 mg/kg) which selectively inhibited MAO A or MAO B, respectively, striatal dopamine was increased while the striatal DOPAC and HVA levels and DOPAC/dopamine ratio were significantly reduced as compared to the values obtained with
-DOPA alone. The two MAO inhibitors also counteracted the increase in the DOPAC and HVA levels and DOPAC/dopamine ratio induced by
-DOPA in the substantia nigra. Thus, both MAO A and MAO B contribute to the metabolism of dopamine when higher levels of this neurotransmitter are generated from
-DOPA in the squirrel monkey. The extent of reduction of dopamine catabolism (as assessed by the decrease in DOPAC and HVA levels) in the striatum and substantia nigra was similar with clorgyline and deprenyl even if the ratio MAO A/MAO B was approximately 1 to 10. This indicates that, though catalyzed by both MAO A and MAO B, dopamine deamination following treatment with
-DOPA preferentially involves MAO A. 相似文献
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8.
Effects of
Experiments involving single-unit recordings and microiontophoresis were carried out in the barrel cortex of awake, adult rats subjected to whisker pairing, an associative learning paradigm where deflections of the recorded neuron's principle vibrissa (S2) are repeatedly paired with those of a non-adjacent one (S1). Whisker pairing with a 300 ms interstimulus interval was applied to 61 cells. In 23 cases, there was no other manipulation whereas in the remaining 38, pairing occurred in the presence of one of three pharmacological agents previously shown to modulate learning, receptive field plasticity and long-term potentiation: N-methyl-
-aspartic acid (NMDA) (n=8), the NMDA receptor antagonist AP5 (n=17) or the nitric oxide synthase inhibitor
-nitro-arginine-N-methyl-ester (
-NAME) (n=13). Non-associative (unpaired) experiments (n=14) and delivery of pharmacological agents without pairing (n=14) served as controls. Changes in neuronal responsiveness to S1 following one of these procedures were calculated and adjusted relative to changes in the responses to S2. On average, whisker pairing alone yielded a 7% increase in the responses to S1. This enhancement differed significantly from the 17% decrease obtained in the non-associative control condition and could not be attributed to variations in the state of the animals because analysis of the cervical and facial muscle electromyograms revealed that periods of increased muscular activity, reflecting heightened arousal, were infrequent (less than 4% of a complete experiment on average) and occurred randomly. The enhancement of the responses to S1 was further increased when whisker pairing was performed in the presence of
-NAME (27%) or NMDA (35%) whereas AP5 reduced it to 1%. During the delivery period, NMDA enhanced both neuronal excitability and responsiveness to S1 whereas AP5 depressed them. However, the effects of both substances disappeared immediately after administration had ended.
-NAME did not affect the level of ongoing activity and responses to S1 significantly. From these data, we concluded that, since the changes in the responses to S1 lasted longer than the periods of both whisker pairing and drug delivery, they were not residual excitatory or inhibitory drug effects on neuronal excitability. Thus, our results indicate that, relative to the unpaired controls, whisker pairing led to a 24% increase in the responsiveness of barrel cortex neurons to peripheral stimulation and that these changes were modulated by the local application of pharmacological agents that act upon NMDA receptors and pathways involving nitric oxide. We can infer that somatosensory cerebral cortex is one site where plasticity emerges following whisker pairing. 相似文献
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9.
Harmaline competitively inhibits [
Harmaline, a β-carboline derivative, is known to produce tremor through a direct activation of cells in the inferior olive. However, the receptor(s) through which harmaline acts remains unknown. It was recently reported that the tremorogenic actions of harmaline could be blocked by the noncompetitive NMDA channel blocker, MK-801. This study examined whether the blockade of harmaline's action, in the rabbit, by MK-801 was due to a pharmacological antagonism at the MK-801 binding site. This was accomplished by measurement of [
]MK-801 binding in membrane fractions derived from tissue containing the inferior olivary nucleus and from cerebral cortex. Harmaline completely displaced saturable [
]MK-801 binding in both the inferior olive and cortex with apparent IC50 values of 60 and 170 μM, respectively. These IC50 values are consistent with the high doses of harmaline required to produce tremor, e.g., 10–30 mg/kg. Non-linear curve fitting analysis of [
]MK-801 saturation experiments indicated that [
]MK-801 bound to a single site and that harmaline's displacement of [
]MK-801 binding to the NMDA receptor was competitive as indicated by a shift in Kd but not in Bmax. In addition, a Schild plot gave a slope that was not significantly different from 1 indicating that harmaline was producing a displacement of [
]MK-801 from its binding site within the NMDA cation channel and not through an action at the glutamate or other allosteric sites on the NMDA receptor. These findings provide in vitro evidence that the competitive blockade of harmaline-induced tremor by MK-801 occurs within the calcium channel coupled to the NMDA receptor. Our hypothesis is that harmaline produces tremor by acting as an inverse agonist at the MK-801 binding site and thus opening the cation channel. 相似文献
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10.
Cardiovascular effects elicited by microinjection of
-S-nitrosocysteine in the nucleus tractus solitarii (NTS) were compared and contrasted with those produced by the dextroisomer, other nitric oxide donors and nitric oxide itself.
-S-nitrosocysteine produced dose-related decreases of arterial pressure and heart rate. In contrast,
-S-nitrosocysteine, S-nitrosoglutathione, glyceryl trinitrate, and sodium nitroprusside produced minimal responses that were not dose-related. Likewise, injection of cystine and nitric oxide, two products of S-nitrosocysteine breakdown, produced no significant response. Headspace analysis using chemiluminescence revealed that
- and
-S-nitrosocysteine released identical amounts of nitric oxide when exposed to homogenates of whole rat brain. Responses to
-S-nitrosocysteine were not affected by local injection of oxyhemoglobin or the nitric oxide synthase inhibitor
-nitroarginine methylester. Although injection of
-cysteine into the NTS produced responses similar to those seen with injection of
-S-nitrosocysteine, blockade of excitatory amino acid receptors with kynurenic acid inhibited responses to cysteine but not those to the nitrosothiol. The study demonstrates that S-nitrosocysteine is biologically active in the NTS. Its action is independent of release of nitric oxide from the nitrosothiol but may be mediated through stereoselective sites on target neurons. 相似文献
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11.
Inhibition of NMDA-induced increase in brain temperature by N-ω-nitro-
Shuichi Hara Toshiji Mukai Fumi Kuriiwa Nobuhisa Iwata Takeshi Yanase Sadao Kano Takahiko Endo 《Brain research》1997,756(1-2)
Intracerebroventricular administration of N-methyl-
-aspartate (NMDA) caused an increase in brain temperature, which appeared rapidly and preceded that in rectal temperature, in urethane-anesthetized rats. The increase in brain temperature was divided into two phases, an early increase and a late increase. Intracerebroventricular indomethacin, a cyclooxygenase inhibitor, completely abolished the NMDA-induced late increase, but not the early increase, in brain temperature. On the other hand, intracerebroventricular N-ω-nitro-
-arginine, a potent inhibitor of nitric oxide synthase, strongly suppressed both the early and the late increases. These findings suggest that both nitric oxide and prostaglandins may be involved in the increase in brain temperature after NMDA receptor activation. 相似文献
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12.
Seizo Sadoshima Tetsuhiko Nagao Yasushi Okada Kenichiro Fujii Setsuro Ibayashi Masatoshi Fujishima 《Brain research》1997,744(2):246-252
The effects of
-arginine (a precursor of nitric oxide, NO) on cerebral blood flow (CBF), cerebrovascular resistance (CVR) and metabolites in the ischemic brain were examined in spontaneously hypertensive rats with bilateral carotid artery occlusion for 30 min followed by 60 min-recirculation. The administration of
-arginine (300 mg/kg, i.v.) increased the CBF by an average of 11 ml·100 g−1·min−1 (P<0.05 vs. at rest), and Nω-nitro-
-arginine (
-NNA, an inhibitor of NO synthase, 5 mg/kg, i.v.) reduced the CBF by 5–6 ml·100 g−1·min−1 with increase in the mean arterial pressure by 26 mmHg. During ischemia the CBF significantly decreased to below 8% of the resting values in all rats. The largest blood flow in postischemic hyperemia was 171±9% of the resting CBF in the rats with
-arginine (P<0.05 vs.
-NNA and saline), followed by 126±5 with saline and 109±3 with
-NNA. The CVR at 60 min of recirculation was 3.291±0.144 mmHg·ml−1·100 g−1·min−1 in the rats with saline, remained low level of 2.711±0.124 with
-arginine (P<0.01 vs.
-NNA and P<0.05 vs. saline) and in contrast, significantly increased to 5.732±0.184 with
-NNA (P<0.01 vs.
-arginine and saline, respectively). Tissue lactate with saline increased 2.3-fold at 60 min of recirculation, whereas the increase was inhibited to 1.4-fold after
-arginine treatment (P<0.01 vs.
-NNA) and in contrast, significantly increased 5.7-fold with
-NNA. The ATP and glucose levels were better preserved in the rats with
-arginine than in those with
-NNA or saline. These findings support that the enhanced postischemic hyperemia is beneficial to the ischemic brain and the administration of
-arginine may be potentially useful for the treatment of acute stroke. 相似文献
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13.
Unique properties of [
In order to investigate possible differences between NMDA receptor-coupled ion channels in the spinal cord and in the cerebral cortex, we have characterized [
]MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine] binding and its regulation by glutamate and glycine in membrane preparations of the rat spinal cord and cerebral cortex. The KD value of [
]MK-801 binding was higher in the spinal cord than in the cerebral cortex, mainly due to a lower association rate constant. When corrected for the concentrations of residual endogenous amino acids, the EC50 values for glycine were lower at spinal NMDA receptors compared to those in the cerebral cortex, whereas the EC50 values for glutamate were similar in both regions. The IC50 values of
-((3)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (
-CPP) were significantly lower in the spinal cord in the presence of saturating concentrations of glutamate. The IC50 values of 7-chloro-4-hydroxy-3-(3-phenoxy)phenyl-2(H)-quinoline (L-701,324) were significantly lower in the spinal cord under all conditions. These results suggest that NMDA receptors in the spinal cord display low affinity for MK-801, which may correspond to a lower affinity of the voltage-dependent Mg2+ block. Furthermore, NMDA receptors in the spinal cord appear to display high sensitivity to glycine and to glutamate and glycine antagonists. 相似文献
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14.
The presence of abundant nitric oxide synthase (NOS) in magnocellular neurons of the rat hypothalamus suggests that nitric oxide (NO) may be involved in controlling the release of oxytocin and vasopressin. To test this possibility, we examined the effect of NO-related drugs on extracellular discharges of 124 supraoptic nucleus (SON) neurons from slices of rat hypothalamus in vitro. Twenty-three (43%) of 53 neurons were inhibited by sodium nitroprusside (SNP), a spontaneous releaser of NO, at 1–3 mM. This inhibition was prevented by preincubation of the slices with 1
hemoglobin, an inactivator of NO (
), whereas hemoglobin alone enhanced neuronal activity in seven (35%) of 20 neurons.
-Arginine (1 mM), a precursor of NO, inhibited neuronal activity in five (36%) of 14 neurons, while
-arginine (1 mM), the inactive counterpart of
-arginine, was ineffective (
). N-
-nitro-
-arginine methyl ester (
-NAME, 10
), an inhibitor of NOS, also enhanced neuronal activity in five (29%) of 17 neurons, while N-
-nitro-
-arginine methyl ester (DNAME, 10
), the inactive enantiomer of
-NAME, was without effect (
). Together, our data show that NO exerts predominantly an inhibitory effect on SON neurons and may serve as a negative feedback loop in controlling release of oxytocin and vasopressin. 相似文献
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15.
A subset of olfactory receptor neurons of the Caribbean spiny lobster Panulirus argus possesses receptors for
-glutamate that can mediate both excitatory and inhibitory responses (P.C. Daniel, M.F. Burgess, C.D. Derby, Responses of olfactory receptor neurons in the spiny lobster to binary mixtures are predictable using a non-competitive model that incorporates excitatory and inhibitory transduction pathways, J. Comp. Physiol. A 178 (1992) 523–536). In this study, we have used biochemical and electrophysiological techniques to understand the role of these receptors in olfactory transduction, and to compare these olfactory glutamate receptors with peripheral and central
-glutamate receptors in other animals. Using a radioligand-binding assay with a membrane-rich preparation from the dendrites of olfactory receptor neurons, we have identified two types of binding sites for
-glutamate. Both sites showed rapid, reversible, and saturable association with radiolabeled
-glutamate, and their Kd values (1 nM and 3 μM) are effective in physiological studies of glutamate-sensitive olfactory neurons, suggesting these binding sites are receptors involved in olfactory transduction. Both sites were completely inhibited by high concentrations of NMDA and
-cysteine, and only partially inhibited by other
-glutamate analogs and odorants. Electrophysiological recordings from
-glutamate-best olfactory receptor neurons showed that NMDA and
-cysteine are both partial agonists and antagonists of glutamate receptors. Together, these results suggest the olfactory
-glutamate receptors of spiny lobsters are novel types of
-glutamate receptors that are functionally important in mediating olfactory responses. 相似文献
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16.
It has been reported that glutamate-induced neurotoxicity is related to an increase in nitric oxide (NO) concentration. An NO-sensitive electrode has been developed to measure NO concentration directly. Using this electrode, we examined NO concentration and neuronal survival after glutamate application in rat cultured cortical neurons. We also examined the effects of NMDA receptor antagonists, MK-801 and ketamine, and the NO synthetase inhibitor,
-NMMA on NO production and neuronal death. After 7 days in culture, application of glutamate (1 mM) or
-arginine (0.3 mM) to the cultured medium increased NO concentration, and decreased the number of anti-microtubule-associated protein 2 positive neurons. Both pretreatment with MK-801 (300 μm) and ketamine (300 μm) prevented glutamate-, but not
-arginine-induced increase in NO concentration and neuronal death.
-NMMA prevented both glutamate- and
-arginine-induced NO production and neuronal death. The nitric oxide donor, S-nitroso-N-acetyl-
,
-penicillamine (SNAP) also caused neuronal death, and MK-801, ketamine and
-NMMA did not prevent SNAP-induced toxicity. We have demonstrated excitatory amino acid-induced changes of NO concentration and the parallel relationship between changes of NO concentration and neuronal death. In conclusion, an increase in NO concentration does induce neuronal death, and the inhibition of the production of NO prevents glutamate-induced neuronal death. 相似文献
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17.
The regulation of dopamine release by 6(R)-tetrahydrobiopterin (BH4) and
-arginine-derived nitric oxide was examined by using a method of superfusion of rat striatum slices in vitro.
-Arginine, which can produce nitric oxide (NO) through the action of NO synthase, induces a concentration-dependent increase of [
] dopamine release in the superfusate of striatum slices. Pretreatment with inhibitors of NO synthase or with inhibitors of BH4 synthesis diminishes the increase of [
] dopamine release mediated by arginine. This increase is almost completely restored following repletion of intracellular BH4 levels by incubation of the slices with 7,8-dihydrobiopterin. Adding exogenous BH4 directly to the superfusion fluid leads to a massive increase in [
] dopamine release which can be inhibited 75% by superoxide dismutase and catalase, but is not inhibited by NG-nitro-arginine, a NO synthase inhibitor, or alpha-methyl-p-tyrosine, a tyrosine hydroxylase inhibitor. The increase of intracellular BH4 concentration by dihydrobiopterin administration causes a small increase of dopamine release which can be partially diminished by NG-nitro-arginine or alpha-methyl-p-tyrosine. It is suggested that the increase of dopamine release stimulated by an enhancement of intracellular BH4 is dependent on its cofactor activity with NO synthase and tyrosine hydroxylase. This study has also demonstrated that BH4 is a regulator of NO-mediated dopamine release in the striatum. 相似文献
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18.
Takehiko Maeda Neng-neng Cheng Toshiaki Kume Satoshi Kaneko Hanae Kouchiyama Akinori Akaike Mutsuaki Ueda Masamichi Satoh Yoshio Goshima Yoshimi Misu 《Brain research》1997,771(1):259
The exposure of cultured rat striatal neurons to
-DOPA caused marked cell death. The
-DOPA cytotoxicity was inhibited by the addition of Mg2+ to and by the removal of Ca2+ from the culture medium, and also by the application of tetrodotoxin. Moreover, prolonged application of
-DOPA increased the glutamate content in the culture medium. These results indicate that
-DOPA produces neurotoxicity by facilitating glutamate release. 相似文献
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19.
In the present study we evaluated the role of NMDA receptors on the pressor and bradycardic responses to
-glutamate (
-Glu) microinjected into the nucleus tractus solitarius (NTS) of unanesthetized rats.
-Glu (1 nmol/100 nl) was microinjected into the NTS before and 10 min after microinjection of phosponovaleric acid (AP-5), a selective NMDA receptor antagonist, into the NTS of three different groups of rats (0.5, 2.0 and 10.0 nmol/100 nl). Microinjection of AP-5 into the NTS produced a dose-dependent reduction in the bradycardic response to
-Glu. However, no significant change in the pressor response to
-Glu was observed. These results indicate that the activation of the cardiovagal component (bradycardia) by
-Glu involves NMDA receptors and suggest that the activation of the sympatho-excitatory component (pressor response) by
-Glu in the commissural NTS is mediated by non-NMDA receptors.© 1997 Elsevier Science B.V. All rights reserved. 相似文献
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20.
Since ATP has been reported to be a potent excitatory transmitter in the mammalian central nervous system (CNS), we studied the neurochemical characters of the binding sites of
,
-methylene ATP, an agonist of P2X receptors, in mouse crude synaptic membranes. ATP and its related compounds inhibited [3H]
,
-methylene ATP binding in a concentration-dependent manner. The potency order in the inhibition of the binding was as follows;
,
-methylene
>
> ATP ≥ ADP >
,
-methylene ATP UTP > 2-methylthio ATP. And adenosine did not affect the binding. The order was different from those reported in peripheral tissues. And Sr2+, Ca2+, Mg2+, and Cd2+ enhanced the binding. These results suggest that
,
-methylene ATP binding sites in CNS have different characters from those in peripheral tissues. 相似文献
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