共查询到20条相似文献,搜索用时 31 毫秒
1.
D. Jantas M. Szymanska B. Budziszewska W. Lason 《Apoptosis : an international journal on programmed cell death》2009,14(7):900-912
Memantine, a clinically used NMDA receptor antagonist possesses neuroprotective properties, but the exact mechanisms of its
beneficial action on neuronal survival are poorly recognized. In the present study, some intracellular mechanisms of memantine
effects on staurosporine-evoked cell death were investigated in primary cortical neurons. Memantine (0.1–2 μM) suppressed
neuronal apoptosis evoked by staurosporine in 7 DIV cortical neurons, whereas other antagonists of NMDA receptor, MK-801 (1 μM)
and AP-5 (100 μM) were ineffective. The anti-apoptotic effects of memantine were not connected with any changes in cytoplasmic
calcium concentration or reactive oxygen species level. The immunoblot analysis showed that the staurosporine induced a decrease
in p-Akt protein kinase level and that this effect was reversed by memantine treatment. Moreover, the PI3-K inhibitors, wortmannin
and LY 294002 attenuated the anti-apoptotic action of memantine on staurosporine-induced cell damage. Furthermore, the ELISA
studies showed increased cellular and released BDNF protein level after combined treatment with memantine and staurosporine.
There was no effect of memantine on the activation and expression of other protein kinases involved in the mechanism of cellular
survival, i.e. ERK1/2, JNK and GSK3-β. The obtained data suggest an NMDAR-independent action of memantine in attenuation of
neuronal apoptosis and point to the engagement of BDNF and PI3-K/Akt pathway in these processes. 相似文献
2.
3.
Premkumar LS 《The Journal of membrane biology》2005,204(3):129-136
The primary target for cocaine is believed to be monoamine transporters because of cocaine’s high-affinity binding that prevents
re-uptake of released neurotransmitter. However, direct interaction with ion channels has been shown to be important for certain
pharmacological/toxicological effects of cocaine. Here I show that cocaine selectively blocks a calcium-dependent K+ channel in hippocampal neurons grown in culture (IC50 = ∼30 μM). Single-channel recordings show that in the presence of cocaine, the channel openings are interrupted with brief closures
(flicker block). As the concentration of cocaine is increased the open-time is reduced, whereas the duration of brief closures
is independent of concentration. The association and dissociation rate constants of cocaine for the neuronal Ca2+-activated K+ channels are 261 ± 37 μM−1s−1 and 11451 ± 1467 s−1. The equilibrium dissociation constant (KB) for cocaine, determined from single-channel parameters, is 43 μM. The lack of voltage dependence of block suggests that cocaine probably binds to a site at the mouth of the pore. Block of
Ca2+-dependent K+ channels by cocaine may be involved in functions that include broadening of the action potential, which would facilitate
transmitter release, enhancement of smooth muscle contraction particularly in blood vessels, and modulation of repetitive
neuronal firing by altering the repolarization and afterhyperpolarization phases of the action potential. 相似文献
4.
5.
N-Methyl-<Emphasis Type="SmallCaps">D</Emphasis>-Aspartate Receptor in Human Prostate Cancer 总被引:1,自引:0,他引:1
Expression of the N-methyl-D-aspartate receptor (NMDAr) and its involvement in cellular proliferation is well-known in tumors of neuronal tissue, such
as glioma and neuroblastoma. We have investigated NMDAr expression in the normal, hyperplastic and neoplastic human prostate
by immunohistochemistry. Low stromal NMDAr immunostaining was observed in 2 of 12 (17%) normal prostate specimens, but epithelial
NMDAr staining was not seen. Of 18 benign prostatic hyperplasia (BPH) specimens, none had stromal NMDAr staining, but 2 had
low and 1 had high epithelial NMDAr immunoreactivity. Moderate to high NMDAr immunostaining was observed in the stroma of
60 of 145 (41%) prostate cancer (PCa) specimens. Epithelial NMDAr staining was low in 26 (18%) and moderate to high in 36
(25%) of 145 PCa specimens. We have also examined the effects of the NMDAr antagonist memantine on the growth of ten human
cancer cell lines: four prostate, two breast and four colon. The NMDAr antagonist memantine inhibited in-vitro growth of all
ten cell lines, with half-maximal growth-inhibition at 5 to 20 μg/ml (23 to 92 μM) memantine. An NMDA agonist, L-cysteinesulfinic acid, stimulated cellular proliferation of all ten cell lines, with maximal growth-stimulation (30% to 75%,
depending on the cell line) observed between doses of 33 to 66 μM. Our data provide evidence for the expression and activity
of NMDAr in prostate cancer. 相似文献
6.
B. Sarkadi A. Tordai L. Homolya O. Scharff G. Gárdos 《The Journal of membrane biology》1991,123(1):9-21
Summary Jurkat and MOLT-4 cultured T lymphoblasts were loaded with low concentrations (30–50 m) of indo-1 and with high concentrations (3.5–4.5mm) of quin-2, respectively, in order to follow the activation of calcium transport pathways after stimulation of the cells by a monoclonal antibody against the T cell antigen receptor (aCD3), or after the addition of thapsigargin, a presumed inhibitor of endoplasmic reticulum calcium pump. In the indo-1 loaded cells the dynamics of the intracellular calcium release and the calcium influx could be studied, while in the quin-2 overloaded cells the changes in cytoplasmic free calcium concentration ([Ca2+]
i
) were strongly buffered and the rate of calcium influx could be quantitatively determined. We found that in Jurkat lymphoblasts, in the absence of external calcium, both aCD3 and thapsigargin induced a rapid calcium release from internal stores, while upon the readdition of external calcium an increased rate of calcium influx could be observed in both cases, aCD3 and thapsigargin released calcium from the same intracellular pools. The calcium influx induced by either agent was of similar magnitude and had a nonadditive character if the two agents were applied simultaneously. As demonstrated in quin-2 overloaded cells, a significant initial rise in [Ca2+]
i
or a pronounced depletion of internal calcium pools was not required to obtain a rapid calcium influx. The activation of protein kinase C by phorbol ester abolished the internal calcium release and the calcium influx induced by aCD3, while having only a small effect on these phenomena when evoked by thapsigargin. Membrane depolarization by gramicidin inhibited the rapid calcium influx in both aCD3- and thapsigargin-treated cells, although it did not affect the internal calcium release produced by either agent. In MOLT-4 cells, which have no functioning antigen receptors, aCD3 was ineffective in inducing a calcium signal, while thapsigargin produced similar internal calcium release and external calcium influx to those observed in Jurkat cells. 相似文献
7.
In in vitro studies on superfused slices obtained from the rat hippocampus and cortex, we found that 50 μM N-methyl-D-aspartate (NMDA)
applied to the slices in the presence of 10 μM glycine for 15 min exerts a significant damaging action to neurons of these
structures. One hour after termination of the action of NMDA, this was manifested in more than a twofold decrease in the synaptic
reactivity of pyramidal neurons of the hippocampal СА1 area and layers II/III of the cerebral cortex. The excitotoxic effect of NMDA was prevented by application of competitive
(D-2-amino-5-phosphonovaleric acid, 50 μM) and noncompetitive (ketamine, 100 μM) blockers of NMDA receptors. A blocker of
glycine-binding sites of NMDA receptors (compound ТСВ 24.15, 10 μM) weakened NMDA-induced damage to the neurons. A competitive
blocker of glutamate АМРА receptors, 6,7-dinitroquinoxaline-2,3-dione (DNQX, 10 μM), and a local anesthetic, lidocaine hydrochloride
(50 μM), did not modify the excitotoxic effect of NMDA. A blocker of voltagedependent L-type calcium channels, verapamil (20
μM), demonstrated some trend to intensification of NMDA excitotoxic action. An inhibitor of tyrosine-protein phosphatases,
sodium vanadate, when i.p. injected into rats in a dose of 15 mg/kg 6 h prior to the electrophysiological experiment, decreased
the damaging action of NMDA. Two-hour-long treatment of cerebral slices with 1 μM genistein, an inhibitor of tyrosine kinases,
weakened the neuroprotective effect of sodium vanadate. Chronic injections (14 days in daily doses of 20 mg/kg) of antidepressants
belonging to different functional classes (imipramine, fluoxetine, and pyrazidol) into rats decreased (similarly to blockers
of NMDA receptors) the excitotoxic action of NMDA receptors. Neuroprotective effects of antidepressants were weakened upon
the action of genistein. We conclude that the neuroprotective activity of antidepressants under conditions of excitotoxic
action of NMDA is mainly determined by an increase in the activity of tyrosine kinases in the cytoplasm and/or neuronal nucleus. 相似文献
8.
Yong-Hong Liu Lian Wang Li-Chun Wei Yuan-Gui Huang Liang-Wei Chen 《Neurochemical research》2009,34(7):1209-1218
Epilepsy is a serious neurological disorder with neuronal loss and spontaneous recurrent seizures, but the neurochemical basis
remains largely unclear. We hypothesize that d-serine, a newly identified endogenous co-agonist of N-methyl-d-aspartate (NMDA) receptor, may trigger excitotoxicity and neuronal damage in epileptogenesis. By using a mouse pilocarpine
model, immunohistochemistry, Fluoro-Jade staining and double-labeling, the present study revealed up-regulation of d-serine expression in a proportion (41%) of neurons in the cerebral cortex and hippocampus. The d-serine-positive neurons occurred at 4 h, reached peak levels at 12–24 h, and gradually went down at 3–14 days. Moreover,
most of d-serine-positive neurons were GABAergic (98%), underwent degenerating death (93%), and were accompanied enhancing phosphorylation
of NMDA receptor subunit 1. This study has provided new evidence that up-regulation of d-serine production might induce GABAergic neuronal degeneration through excitotoxic mechanism in the pilocarpine model and
may be involved in early pathogenesis and recurrent seizure of chronic epilepsy.
Ms. L. Wang is on leave from Department of Neurology, Kunming General Hospital of Chengdu Military Region, China. 相似文献
9.
l-Glutamic acid (l-Glu) and other excitatory amino acids and amino acid analogs enhanced [35S]thiocyanate (SCN–) uptake in isolated-resealed synaptic membrane vesicles. The SCN– uptake was used as a measure of membrane depolarization to evaluate the characteristics of functional excitatory amino acid receptors in the synaptic membranes.N-Methyl-d-aspartate (NMDA) andl-Glu produced additive effects on SCN– accumulation indicating the presence of distinctl-Glu and NMDA receptors. On the other hand, kainic acid (KA) andl-Glu shared either common receptor sites or ion channels. The effects of antagonists on NMDA,l-Glu, and KA stimulation of SCN– influx were consistent with previously reported electrophysiologic observations in intact neurons. 相似文献
10.
In this study, weinvestigated the mechanism that links activation ofN-methyl-D-aspartate (NMDA) receptors to inhibition ofvoltage-gated sodium channels in isolated catfish cone horizontal cells. NMDA channels were activated in voltage-clamped cells incubated in low-calcium saline or dialyzed with the calcium chelator BAPTA todetermine that calcium influx through NMDA channels is required forsodium channel modulation. To determine whether calcium influx throughNMDA channels triggers calcium-induced calcium release (CICR), cellswere loaded with the calcium-sensitive dye calcium green 2 and changesin relative fluorescence were measured in response to NMDA. Responseswere compared with measurements obtained when caffeine depleted stores.Voltage-clamp studies demonstrated that CICR modulated sodium channelsin a manner similar to that of NMDA. Blocking NMDA receptors with AP-7,blocking CICR with ruthenium red, depleting stores with caffeine, ordialyzing cells with calmodulin antagonists W-5 or peptide 290-309all prevented sodium channel modulation. These results support thehypothesis that NMDA modulation of voltage-gated sodium channels inhorizontal cells requires CICR and activation of a calmodulin-dependentsignaling pathway. 相似文献
11.
The uptake of 3H-labeled choline by a suspension of isolated type II epithelial cells from rat lung has been studied in a Ringer medium.
Uptake was linear for 4 min at both 0.1 μm and 5.0 μm medium choline; at 5 μm, only 10% of the label was recovered in a lipid fraction. Further experiments were conducted at the low concentration (0.1
μm), permitting characterization of the properties of high-affinity systems. Three fractions of choline uptake were detected:
(i) a sodium-dependent system that was totally inhibited by hemicholinium-3 (HC-3); (ii) a sodium-independent uptake, when
Na+ was replaced by Li+, K+ or Mg2+, inhibited by HC-3; (iii) a residual portion persisting in the absence of Na+ and unaffected by HC-3. Choline uptake was sigmoidally related to the medium Na+ concentration. Kinetic properties of the uptake of 0.1 μm
3H-choline in the presence and absence of medium Na+ were examined in two ways. (a) Inhibition by increasing concentrations of unlabeled choline (0.5–100 μm) was consistent with the presence of two Michaelis-Menten-type systems in the presence of Na+; a Na+-dependent portion (a mean of 0.52 of the total) had a K
m
for choline of 1.5 μm while K
m
in the absence of Na+ (Li+ substituting) was 18.6 μm. (b) Inhibition by HC-3 (0.3–300 μm) gave Ki values of 1.7 μm and 5.0 μm HC-3 for the Na+-dependent and -independent fractions. The apparent K
m
of the Na+-dependent uptake is lower than that reported previously for lung-derived cells and is in the range of the K
m
values reported for high-affinity, Na+-dependent choline uptake by neuronal cells.
Received: 18 February 1997/Revised: 7 December 1997 相似文献
12.
Polysaccharides from Wolfberry Antagonizes Glutamate Excitotoxicity in Rat Cortical Neurons 总被引:1,自引:0,他引:1
Yuen-Shan Ho Man-Shan Yu Suet-Yi Yik Kwok-Fai So Wai-Hung Yuen Raymond Chuen-Chung Chang 《Cellular and molecular neurobiology》2009,29(8):1233-1244
Glutamate excitotoxicity is involved in many neurodegenerative diseases including Alzheimer’s disease (AD). Attenuation of
glutamate toxicity is one of the therapeutic strategies for AD. Wolfberry (Lycium barbarum) is a common ingredient in oriental cuisines. A number of studies suggest that wolfberry has anti-aging properties. In recent
years, there is a trend of using dried Wolfberry as food supplement and health product in UK and North America. Previously,
we have demonstrated that a fraction of polysaccharide from Wolfberry (LBA) provided remarkable neuroprotective effects against
beta-amyloid peptide-induced cytotoxicity in primary cultures of rat cortical neurons. To investigate whether LBA can protect
neurons from other pathological factors such as glutamate found in Alzheimer brain, we examined whether it can prevent neurotoxicity
elicited by glutamate in primary cultured neurons. The glutamate-induced cell death as detected by lactate dehydrogenase assay
and caspase-3-like activity assay was significantly reduced by LBA at concentrations ranging from 10 to 500 μg/ml. Protective
effects of LBA were comparable to memantine, a non-competitive NMDA receptor antagonist. LBA provided neuroprotection even
1 h after exposure to glutamate. In addition to glutamate, LBA attenuated N-methyl-d-aspartate (NMDA)-induced neuronal damage. To further explore whether LBA might function as antioxidant, we used hydrogen
peroxide (H2O2) as oxidative stress inducer in this study. LBA could not attenuate the toxicity of H2O2. Furthermore, LBA did not attenuate glutamate-induced oxidation by using NBT assay. Western blot analysis indicated that
glutamate-induced phosphorylation of c-jun N-terminal kinase (JNK) was reduced by treatment with LBA. Taken together, LBA
exerted significant neuroprotective effects on cultured cortical neurons exposed to glutamate. 相似文献
13.
Glutathione (γ-glutamylcysteinylglycine, GSH and oxidized glutathione, GSSG), may function as a neuromodulator at the glutamate
receptors and as a neurotransmitter at its own receptors. We studied now the effects of GSH, GSSG, glutathione derivatives
and thiol redox agents on the spontaneous, K+- and glutamate-agonist-evoked releases of [3H]dopamine from mouse striatal slices. The release evoked by 25 mM K+ was inhibited by GSH, S-ethyl-, -propyl-, -butyl- and pentylglutathione and glutathione sulfonate. 5,5′-Dithio-bis-2-nitrobenzoate (DTNB) and l-cystine were also inhibitory, while dithiothreitol (DTT) and l-cysteine enhanced the K+-evoked release. Ten min preperfusion with 50 μM ZnCl2 enhanced the basal unstimulated release but prevented the activation of K+-evoked release by DTT.
Kainate and 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) evoked dopamine release but the other glutamate receptor
agonists N-methyl-d-aspartate (NMDA), glycine (1 mM) and trans-1-aminocyclopentane-1,3-dicarboxylate (t-ACPD, 0.5 mM), and the modulators GSH, GSSG, glutathione sulfonate, S-alkyl-derivatives of glutathione, DTNB, cystine, cysteine and DTT (all 1 mM) were without effect. The release evoked by 1 mM
glutamate was enhanced by 1 mM GSH, while GSSG, glutathionesulfonate and S-alkyl derivatives of glutathione were generally without effect or inhibitory. NMDA (1 mM) evoked release only in the presence
of 1 mM GSH but not with GSSG, other peptides or thiol modulators. l-Cysteine (1 mM) enhanced the glutamate-evoked release similarly to GSH. The activation by 1 mM kainate was inhibited by S-ethyl-, -propyl-, and -butylglutathione and the activation by 0.5 mM AMPA was inhibited by S-ethylglutathione but enhanced by GSSG.
Glutathione alone does not directly evoke dopamine release but may inhibit the depolarization-evoked release by preventing
the toxic effects of high glutamate, and by modulating the cysteine–cystine redox state in Ca2+ channels. GSH also seems to enhance the glutamate-agonist-evoked release via both non-NMDA and NMDA receptors. In this action,
the γ-glutamyl and cysteinyl moieties of glutathione are involved. 相似文献
14.
中国科学 《中国科学:生命科学英文版》2000,43(6):655-662
Using nystatin-perforated whole-cell recording configuration, the modulatory effect of N-methyl-D-aspartate (NMDA) on γ-aminobutyric
acid (GABA)-activated whole-cell currents was investigated in neurons freshly dissociated from the rat sacral dorsal commissural
nucleus (SDCN). The results showed that: (i) NMDA suppressed GABA-and muscimol (Mus)-activated currents (Igaba and IMus), respectively in the Mg2+-free external solution containing 1 μmol/L glycine at a holding potential (V
H
) of −40 mV in SDCN neurons. The selective NMDA receptor antagonist, D-2-amino-5-phosphonovaleric acid (APV, 100 γmol/L),
inhibited the NMDA-evoked currents and blocked the NMDA-induced suppression of Igaba; (ii) when the neurons were incubated in a Ca2+-free bath or pre-loaded with a membrane-permeable Ca2+ chelator, BAPTA AM (10 μmol/L), the inhibitory effect of NMDA on IGAba disappeared. Cd2+ (10 μmol/L) or La3+ (30 μmol/L), the non-selective blockers of voltage-dependent calcium channels, did not affect the suppression of Igaba by NMDA application; (iii) the suppression of IGAba by NMDA was inhibited by KN-62, a calcium/calmodulin-dependent protein kinase II (CaMKII) inhibitor. These results indicated
that the inhibition of GABA response by NMDA is Ca2+-dependent and CaMKII is involved in the process of the Ca2+-dependent inhibition. 相似文献
15.
《Cell communication & adhesion》2013,20(5):441-453
L1, NCAM and N-cadherin are cell adhesion molecules (CAMs), present on neuronal growth cones, which promote cell-contact dependent axonal growth by activating a second messenger pathway in neurons that requires calcium influx through L- and N- type calcium channels. In the present study we show that two of these CAMs, (L1 and N-cadherin) can stimulate neurite regeneration from axotomised adult dorsal root ganglion (DRG) neurons cultured in vitro and that this response can be fully inhibited by agents that block or negate the effect of calcium influx into the neurons. However although the response required calcium influx into neurons, it was not associated with an increase in the steady state levels of calcium in neuronal growth cones. These results suggest that small localised changes, or increases in the rate of calcium cycling, in growth cones and/or filopodia, are more important for regulating axonal growth than changes in the steady-state level of calcium. 相似文献
16.
Green D Pace SM Hurne AM Waring P Hart JD Dulhunty AF 《The Journal of membrane biology》2000,175(3):223-233
Interactions between the reactive disulfide fungal metabolite, gliotoxin (GTX), and rabbit skeletal ryanodine receptor (RyR)
calcium release channels have been examined. RyRs in terminal cisternae vesicles formed a covalent complex with 100 μm
35S-GTX, which was reversed by 1 mm dithiothreitol (DTT) or 1 mm glutathione. GTX (80–240 μm), added to either cytoplasmic (cis) or luminal (trans) solutions, increased the rate of Ca2+ release from SR vesicles and the frequency of opening of single RyR channels in lipid bilayers. Channel activation was reversed
upon addition of 2 mm DTT to the cis solution, showing that the activation was due to an oxidation reaction (2 mm DTT added to the cis solution in the absence of GTX did not affect RyR activity). Furthermore, RyRs were not activated by trans GTX if the cis chamber contained DTT, suggesting that GTX oxidized a site in or near the membrane. In contrast to cis DTT, 2 mm DTT in the trans solution increased RyR activity when added either alone or with 200 μm
trans GTX. The results suggest that (i) GTX increases RyR channel activity by oxidizing cysteine residues that are close to the
membrane and located on RyR, or associated proteins, and (ii) a disulfide bridge or nitrosothiol, accessible only from the
luminal solution, normally suppresses RyR channel activity. Some of the actions of GTX in altering Ca2+ homeostatsis might depend on its modification of RyR calcium channels.
Received: 12 November 1999/Revised: 14 March 2000 相似文献
17.
Florian Wegner† Robert Kraft‡ Kathy Busse§ Grit Schaarschmidt‡ Wolfgang Härtig¶ Sigrid C. Schwarz Johannes Schwarz† 《Journal of neurochemistry》2009,111(1):204-216
Human midbrain‐derived neural progenitor cells (NPCs) may serve as a continuous source of dopaminergic neurons for the development of novel regenerative therapies in Parkinson’s disease. However, the molecular and functional characteristics of glutamate receptors in human NPCs are largely unknown. Here, we show that differentiated human mesencepahlic NPCs display a distinct pattern of glutamate receptors. In whole‐cell patch‐clamp recordings, l ‐glutamate and NMDA elicited currents in 93% of NPCs after 3 weeks of differentiation in vitro. The concentration‐response plots of differentiated NPCs yielded an EC50 of 2.2 μM for glutamate and an EC50 of 36 μM for NMDA. Glutamate‐induced currents were markedly inhibited by memantine in contrast to 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX) suggesting a higher density of functional NMDA than alpha‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate (AMPA)/kainate receptors. NMDA‐evoked currents and calcium signals were blocked by the NR2B‐subunit specific antagonist ifenprodil indicating functional expression of NMDA receptors containing subunits NR1 and NR2B. In calcium imaging experiments, the blockade of voltage‐gated calcium channels by verapamil abolished AMPA‐induced calcium responses but only partially reduced NMDA‐evoked transients suggesting the expression of calcium‐impermeable, GluR2‐containing AMPA receptors. Quantitative real‐time PCR showed a predominant expression of subunits NR2A and NR2B (NMDA), GluR2 (AMPA), GluR7 (kainate), and mGluR3 (metabotropic glutamate receptor). Treatment of NPCs with 100 μM NMDA in vitro during proliferation (2 weeks) and differentiation (1 week) increased the amount of tyrosine hydroxylase‐immunopositive cells significantly, which was reversed by addition of memantine. These data suggest that NMDA receptors in differentiating human mesencephalic NPCs are important regulators of dopaminergic neurogenesis in vitro. 相似文献
18.
The effects of sialylcholesterol, a synthetic ganglioside analogue, on cholinergic synaptic functions were investigated using synaptosomes prepared from C57BL/6 mouse brain cortices. Addition of -sialylcholesterol stimulated high K (50mm)-evoked acetylcholine (ACh) release from synaptosomes at concentrations ranging from 1 to 5 µm. The -anomer of the sialyl compound also increased the neurotransmitter release at 5 µm, but the effect was much smaller than that of the -anomer. Beta-sialylcholesterol appeared to increase high-affinity choline uptake and ACh synthesis, resulting in an increment in the release of ACh. On the other hand, -sialylcholesterol did not change the synthetic rate of ACh, and instead it increased the depolarization-induced influx of calcium ions into synaptosomes, while the -anomer did not affect the divalent cation influx. The enhanced calcium influx is thought to increase ACh release from synaptosomes treated with -sialylcholesterol. These results imply that the two anomers of sialylcholesterol may modulate the synaptic membrane machinery differently, that is, the -anomer may activate voltage-dependent calcium channels and the -anomer may facilitate high-affinity choline uptake.In order to evaluate the ameliorating effect of sialylcholesterol, -sialylcholesterol was applied to the synaptosomes from aged mice (34 months old), which have been shown to have a decreased ACh release (Tanakaet al., 1995,J Neurosci Res, in press [1]). The reduced neurotransmitter release recovered to the levels of younger animals, suggesting that sialylcholesterol might have a potential therapeutic use for restoring synaptic function that occurs in aged brains. 相似文献
19.
The modulation of the calmodulin-induced inhibition of the calcium release channel (ryanodine receptor) by two sulfhydryl
oxidizing compounds, 4-(chloromercuri)phenyl–sulfonic acid (4-CMPS) and 4,4′-dithiodipyridine (4,4′-DTDP) was determined by
single channel current recordings with the purified and reconstituted calcium release channel from rabbit skeletal muscle
sarcoplasmic reticulum (HSR) and [3H]ryanodine binding to HSR vesicles. 0.1 μm CaM reduced the open probability (P
o
) of the calcium release channel at maximally activating calcium concentrations (50–100 μm) from 0.502 ± 0.02 to 0.137 ± 0.022 (n= 28), with no effect on unitary conductance. 4-CMPS (10–40 μm) and 4,4′-DTDP (0.1–0.3 mm) induced a concentration dependent increase in P
o (> 0.9) and caused the appearance of longer open states. CaM shifted the activation of the calcium release channel by 4-CMPS
or 4,4′-DTDP to higher concentrations in single channel recordings and [3H]ryanodine binding. 40 μm 4-CMPS induced a near maximal (P
o
> 0.9) and 0.3 mm 4,4′-DTDP a submaximal (P
o
= 0.74) channel opening in the presence of CaM, which was reversed by the specific sulfhydryl reducing agent DTT. Neither
4-CMPS nor 4,4′-DTDP affected Ca-[125I]calmodulin binding to HSR. 1 mm MgCl2 reduced P
o
from 0.53 to 0.075 and 20–40 μm 4-CMPS induced a near maximal channel activation (P
o
> 0.9). These results demonstrate that the inhibitory effect of CaM or magnesium in a physiological concentration is diminished
or abolished at high concentrations of 4-CMPS or 4,4′-DTDP through oxidation of activating sulfhydryls on cysteine residues
of the calcium release channel.
Received: 22 July 1999/Revised: 15 November 1999 相似文献
20.
E. López J. Hernandez C. Arce S. Cañadas M. J. Oset-Gasque M. P. González 《Neurochemical research》2010,35(9):1478-1486
The purpose of this paper was to examine the function of N-methyl-D-aspartate (NMDA) glutamate receptor in cortical neurons
on amino acid neurotransmitters release as well as the fraction of neurons implicated in the response of this receptor. Local
stimulation of these cells at different concentrations of NMDA, agonist of this ionotropic glutamate receptor, produced a
dose dependent release of aspartate, glutamate, glycine and GABA. These effects were blocked by DAP5, an antagonist of the
NMDA receptor. The amino acid Ca2+ dependent release mediated by the NMDA receptor, is induced by the opening of voltage-dependent Ca2+ channels that this receptor promotes. Ca++ movements were explored in single cells loaded with fura-2. When single cells were stimulated with 100 μM NMDA, the calcium
recording performed showed that 82% of the cells responded to this agonist increasing the intracellular calcium concentration,
although the amplitude of these increments was variable. The results suggest that NMDA-elicited neurotransmitter release from
cortical neurons involves Ca2+-dependent and Ca2+-independent components, as well as neuron depolarisation, and different VDCC subtypes of N, P/Q or L depending of the amino
acid neurotransmitter release elicited by this receptor. 相似文献