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1.
Adenosine triphosphate (ATP) is coreleased with catecholamines from adrenal medullary chromaffin cells in response to sympathetic
nervous system stimulation and may regulate these cells in an autocrine or paracrine manner. Increases in extracellular signal-regulated
kinase (ERK) 1/2 phosphorylation were observed in response to ATP stimulation of bovine chromaffin cells. The signaling pathway
involved in ATP-mediated ERK1/2 phosphorylation was investigated via Western blot analysis. ATP and uridine 5′-triphosphate
(UTP) increased ERK1/2 phosphorylation potently, peaking between 5 and 15 min. The mitogen-activated protein kinase (MAPK/ERK)-activating
kinase (MEK) inhibitor PD98059 blocked this response. UTP, which is selective for G-protein-coupled P2Y receptors, was the
most potent agonist among several nucleotides tested. Adenosine 5′-O-(3-thio) triphosphate (ATPγS) and ATP were also potent
agonists, characteristic of the P2Y2 or P2Y4 receptor subtypes, whereas agonists selective for P2X receptors or other P2Y receptor subtypes were weakly effective. The
receptor involved was further characterized by the nonspecific P2 antagonists suramin and reactive blue 2, which each partially
inhibited ATP-mediated ERK1/2 phosphorylation. Inhibitors of protein kinase C (PKC), protein kinase A (PKA), Ca2+/calmodulin-dependent protein kinase II (CaMKII), and phosphoinositide-3 kinase (PI3K) had no effect on ATP-mediated ERK1/2
phosphorylation. The Src inhibitor PP2, epidermal growth factor receptor (EGFR) inhibitor AG1478, and metalloproteinase inhibitor
GM6001 decreased ATP-mediated ERK1/2 phosphorylation. These results suggest nucleotide-mediated ERK1/2 phosphorylation is
mediated by a P2Y2 or P2Y4 receptor, which stimulates metalloproteinase-dependent transactivation of the EGFR. 相似文献
2.
Role of P2 purinergic receptors in synaptic transmission under normoxic and ischaemic conditions in the CA1 region of rat hippocampal slices 总被引:3,自引:3,他引:0
The role of ATP and its stable analogue ATPγS [adenosine-5′-o-(3-thio)triphosphate] was studied in rat hippocampal neurotransmission
under normoxic conditions and during oxygen and glucose deprivation (OGD). Field excitatory postsynaptic potentials (fEPSPs)
from the dendritic layer or population spikes (PSs) from the soma were extracellularly recorded in the CA1 area of the rat
hippocampus. Exogenous application of ATP or ATPγS reduced fEPSP and PS amplitudes. In both cases the inhibitory effect was
blocked by the selective A1 adenosine receptor antagonist DPCPX (8-cyclopentyl-1,3-dipropylxanthine) and was potentiated by different ecto-ATPase inhibitors:
ARL 67156 (6-N,N-diethyl-D-β,γ-dibromomethylene), BGO 136 (1-hydroxynaphthalene-3,6-disulfonate) and PV4 [hexapotassium dihydrogen monotitanoundecatungstocobaltate(II)
tridecahydrate, K6H2[TiW11CoO40]·13H2O]. ATPγS-mediated inhibition was reduced by the P2 antagonist suramin [8-(3-benzamido-4-methylbenzamido)naphthalene-1,3,5-trisulfonate]
at the somatic level and by other P2 blockers, PPADS (pyridoxalphosphate-6-azophenyl-2′,4′-disulfonate) and MRS 2179 (2′-deoxy-N
6-methyladenosine 3′,5′-bisphosphate), at the dendritic level. After removal of both P2 agonists, a persistent increase in
evoked synaptic responses was recorded both at the dendritic and somatic levels. This effect was prevented in the presence
of different P2 antagonists. A 7-min OGD induced tissue anoxic depolarization and was invariably followed by irreversible
loss of fEPSP. PPADS, suramin, MRS2179 or BBG (brilliant blue G) significantly prevented the irreversible failure of neurotransmission
induced by 7-min OGD. Furthermore, in the presence of these P2 antagonists, the development of anoxic depolarization was blocked
or significantly delayed. Our results indicate that P2 receptors modulate CA1 synaptic transmission under normoxic conditions
by eliciting both inhibitory and excitatory effects. In the same brain region, P2 receptor stimulation plays a deleterious
role during a severe OGD insult. 相似文献
3.
Neuroprotective effect of GMP in hippocampal slices submitted to an in vitro model of ischemia 总被引:2,自引:0,他引:2
1. Guanosine-5-monophosphate (GMP) was evaluated as a neuroprotective agent against the damage observed in rat hippocampal slices submitted to an in vitro model of ischemia with or without the presence of the ionotropic glutamate receptor agonist, Kainic acid (KA).2. Cellular injury was evaluated by MTT reduction, lactate dehydrogenase (LDH) release assay, and measurement of intracellular ATP levels.3. In slices submitted to ischemic conditions, 1 mM GMP partially prevented the decrease in cell viability induced by glucose and oxygen deprivation and the addition of KA.4. KA or N-methyl-D-aspartate (NMDA) receptor antagonists, -D-glutamylamino-methylsulfonate (GAMS) or (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801, 20 M) also prevented toxicity in hippocampal slices under ischemic conditions, respectively.5. The association of GMP with GAMS or MK-801 did not induce additional protection than that observed with GMP or that classical glutamate receptor antagonists alone.6. GMP, probably by interacting with ionotropic glutamate receptors, attenuated the damage caused by glucose and oxygen deprivation in hippocampal slices. This neuroprotective action of GMP in this model of excitotoxicity is of outstanding interest in the search for effective therapies against ischemic injury. 相似文献
4.
Duhant X Suarez Gonzalez N Schandené L Goldman M Communi D Boeynaems JM 《Purinergic signalling》2005,1(4):377-381
We have previously reported that ATPγS, a slowly hydrolyzed analog of ATP, inhibits the activation of human CD4+ T lymphocytes by anti-CD3 and anti-CD28 mAb. In this report we have partially characterized the signaling mechanisms involved
in this immunosuppressive effect. ATPγS had no inhibitory effect on CD4+ T-cell activation induced by PMA and anti-CD28, indicating that it acts proximally to the TCR. It had no effect on the calcium
rise induced by CD3/CD28 stimulation, but inhibited the phosphorylation of three kinases, ERK2, p38 MAPK and PKB, that play
a key role in the activation of T cells. The receptor involved in these actions remains unidentified. 相似文献
5.
In a dissociated culture of rat hippocampal neurons (14 to 24 daysin vitro), modulation effects of glutamate on GABAA-ergic inhibitory transmission were studied with the use of simultaneous patch-clamp whole-cell recording from monosynaptically
connected neuron pairs. In all experiments (n=49), 1.5-min-long or longer extracellular application of 0.5 to 100 μM glutamate suppressed evoked inhibitory postsynaptic
currents (IPSC). This suppression usually included fast (seconds) and slow (τ=1.3 min) phases. In 83.7% of the cases studied,
IPSC did not return to the control values during the entire subsequent recording period (from 10 to 64 min). When glutamate
was applied in the presence of blockers of glutamate ionotropic receptors, DL-APV or CNQX, the fast phase of the effect was
removed, while some suppression of inhibitory neuronal responses, although weaker, was preserved (n=19); in most cases (73.3%) this residual suppression was slow and long-lasting. It is concluded that both types of glutamate
receptors, ionotropic and metabotropic, are involved in modulation of GABAA-ergic synaptic transmission. The first above receptor type provides fast and reversible suppression, while the effect provided
by the second type is slow and long-lasting. 相似文献
6.
In addition to their role in orchestrating body and tentacle contractions, hydra’s nerves control the behavior of nematocysts;
precisely how is still a work in progress. There are strong indications that the classical neurotransmitters, glutamate and
GABA (γ-amino-butyric acid), play an essential role in effecting stenotele and desmoneme discharge. In experiments on isolated
tentacles of Hydra vulgaris, in which cnidocils were mechanically deflected with a piezo-electrically-driven glass micropipette, stenoteles and desmonemes
respond to differences in applied force in a dose-dependent manner. GABA, working through its metabotropic receptor, appears
to be involved with the recruitment of desmonemes. Desmonemes in distant battery cells or in another part of a given battery
cell were discharged by stimulating a desmoneme cnidocil in the presence of bath-applied GABA or its metabotropic agonist,
baclofen. The effect was blocked by phaclofen, its metabotropic antagonist. Neither GABA nor baclofen affected stenotele discharge.
GABAA agonists had no effect on nematocyst discharge. Glutamate caused a significant increase in number of stenoteles responding
to direct mechanical stimuli, but did not effect desmoneme discharge. The effect was mimicked by NMDA (n-methyl-d-aspartate) together with kainate, or by NMDA plus AMPA (amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid), but not with
any ionotropic agonist alone. The effect was blocked by D-AP 5 (d- (−)–2-amino–5-phosphopentanoic acid), a specific NMDA antagonist, or CNQX (6-cyano-7-nitroquinoxaline-2,3-dione), a specific
kainate/AMPA antagonist. A glutamatergic mechanism working through ionotropic glutamate receptors appears to lower the firing
threshold of stenoteles, perhaps␣by permitting the entry of Ca2+ into the cell through the early evolved NMDA/kainite/AMPA mechanism. 相似文献
7.
I. I. Abramets Yu. V. Kuznetsov I. M. Samoilovich L. Ya. Zin’kovskaya 《Neurophysiology》1999,31(4):227-232
In experiments performed on rat transversial slices of the rat dorsal hippocampus, we found that high-frequency tetanic stimulation
of the mossy fibers (MF) and short-term action of 1 μM kainic acid on the slices resulted in long-term potentiation of the
population spikes evoked inCA3 pyramidal neurons by single stimuli applied to the MF. The tetanus-and kainate-induced potentiations of synaptic transmission
were accompanied by a decrease in the degree of paired facilitation at a 50-msec-long interstimulus interval; they were additive,
prevented by 10 μM CNQX, a competitive antagonist of AMPA/kainate receptors, and insensitive to 100 μM ketamine, a noncompetitive
antagonist of NMDA-glutamate receptors. Both types of potentiation were enhanced by 10 μM (1S, 3R)-ACPD, an agonist of metabotropic
glutamate receptors, as well as by 1 μM pyracetam or 50 μM dichlothiazide, substances weakening AMPA/kainate receptor desensitization.
The effects produced by high-frequency tetanic stimulation of the MF and by kainic acid were prevented by 50 μM polymixin
B, a protein kinase C blocker, and weakened by 10 μM trifluoroperazine, a calmodulin inhibitor, or 1 μM pirenzepine, an M1
acetylcholine receptor blocking agent. In total, the above data suggest that the tetanus- and kainate-induced potentiations
of transmission in the synapses formed by the MF and dendrites ofCA3 pyramidal neurons are due to the combined activation of pre-synaptic high-affinity kainate-preferring receptors, located
in the membranes of the MF varicosities, and post-synaptic phosphoinositide metabolism-coupled metabotropic glutamate receptors
and 1 and M1 acetylcholine receptors. This activation results in a significant increase in the activity of epsilon-form protein
kinase C, phosphorylation of protein substrates involved in vesicular glutamate release from the MF varicosities, and long-term
enhancement of presynaptic glutamate release. 相似文献
8.
Wormser C Pore SA Elperin AB Silverman LN Light DB 《The Journal of membrane biology》2011,242(2):75-87
This study examined the role of a P2 receptor and arachidonic acid (AA) in regulatory volume decrease (RVD) by American alligator
red blood cells (RBCs). Osmotic fragility was determined optically, mean cell volume was measured by electronic sizing, and
changes in intracellular Ca2+ concentration were visualized using fluorescence microscopy. Gadolinium (50 μM), hexokinase (2.5 U/ml), and suramin (100 μM)
increased osmotic fragility, blocked volume recovery after hypotonic shock, and prevented a rise in intracellular Ca2+ that normally occurs during cell swelling. The P2X antagonists PPADS (50 μM) and TNP-ATP (10 μM) also increased fragility
and inhibited volume recovery. In contrast, ATPγS (10 μM), α,β-methylene-ATP (50 μM) and Bz-ATP (50 μM) had the opposite effect,
whereas 2-methylthio-ATP (50 μM) and UTP (10 μM) had no effect. In addition, the phospholipase A2 (PLA2) inhibitors ONO-RS-082 (10 μM), chlorpromazine (10 μM), and isotetrandrine (10 μM) increased osmotic fragility and blocked
volume recovery, whereas AA (10 μM) and its nonhydrolyzable analog eicosatetraynoic acid (ETYA, 10 μM) had the reverse effect.
Further, AA (10 μM), but not ATPγS (10 μM), prevented the inhibitory effect of a low Ca2+-EGTA Ringer on RVD, whereas both AA (10 μM) and ATPγS (10 μM) caused cell shrinkage under isosmotic conditions. In conclusion,
our results are consistent with the presence of a P2-like receptor whose activation stimulated RVD. In addition, AA also was
important for volume recovery. 相似文献
9.
The honeybee, Apis mellifera, is a valuable model system for the study of olfactory coding and its learning and memory capabilities. In order to understand
the synaptic organisation of olfactory information processing, the transmitter receptors of the antennal lobe need to be characterized.
Using whole-cell patch-clamp recordings, we analysed the ligand-gated ionic currents of antennal lobe neurons in primary cell
culture. Pressure applications of acetylcholine (ACh), γ-amino butyric acid (GABA) or glutamate induced rapidly activating
ionic currents. The ACh-induced current flows through a cation-selective ionotropic receptor with a nicotinic profile. The
ACh-induced current is partially blocked by α-bungarotoxin. Epibatidine and imidacloprid are partial agonists. Our data indicate
the existence of an ionotropic GABA receptor which is permeable to chloride ions and sensitive to picrotoxin (PTX) and the
insecticide fipronil. We also identified the existence of a chloride current activated by pressure applications of glutamate.
The glutamate-induced current is sensitive to PTX. Thus, within the honeybee antennal lobe, an excitatory cholinergic transmitter
system and two inhibitory networks that use GABA or glutamate as their neurotransmitter were identified. 相似文献
10.
The influence of glutamate and agonists of its ionotropic receptors on free radical formation in rat brain synaptosomes was
investigated using the fluorescent dye DCFDA. Glutamate at concentrations of 100 μM and 1 mM increased the production of reactive
oxygen species. This phenomenon was eliminated by removing calcium from the incubation medium. Addition of NMDA (100 μM) or
kainate (100 μM) to a suspension of synaptosomes also led to free radical formation. The influence of glutamate receptor agonists
was blocked by the specific antagonists MK-801 and NBQX. Thus, activation of NMDA and AMPA/kainate receptors can lead to oxidative
stress in neuronal presynaptic endings. 相似文献
11.
Cystinosis, an inherited disease caused by a defect in the lysosomal cystine transporter (CTNS), is characterized by renal
proximal tubular dysfunction. Adenosine triphosphate (ATP) depletion appears to be a key event in the pathophysiology of the
disease, even though the manner in which ATP depletion occurs is still a puzzle. We present a model that explains how a futile
cycle that is generated between two ATP-utilizing enzymes of the γ-glutamyl cycle leads to ATP depletion. The enzyme γ-glutamyl cysteine synthetase (γ-GCS), in the absence of cysteine, forms 5-oxoproline (instead of the normal substrate, γ-glutamyl cysteine) and the 5-oxoproline is converted into glutamate by the ATP-dependant enzyme, 5-oxoprolinase. Thus, in
cysteine-limiting conditions, glutamate is cycled back into glutamate via 5-oxoproline at the cost of two ATP molecules without
production of glutathione and is the cause of the decreased levels of glutathione synthesis, as well as the ATP depletion
observed in these cells. The model is also compatible with the differences seen in the human patients and the mouse model
of cystinosis, where renal failure is not observed. 相似文献
12.
We recently reported that ATP is released from Necturus erythrocytes via a conductive pathway during hypotonic swelling and that extracellular ATP potentiates regulatory volume
decrease (RVD). This study was designed to determine whether extracellular ATP exerts its effect via a purinoceptor. This
was accomplished using three different experimental approaches: 1) hemolysis studies to examine osmotic fragility, 2) a Coulter
counter to assess RVD, and 3) the whole-cell patch-clamp technique to measure membrane currents. We found extracellular ATP
and ATPγS, two P2 agonists, decreased osmotic fragility, enhanced cell volume recovery in response to hypotonic shock, and
increased whole-cell currents. In addition, 2-methylthio-ATP potentiated RVD. In contrast, UTP, α,β-methylene-ATP, and 2′-&
3′-O-(4-benzoyl-benzoyl) adenosine 5′-triphosphate and the P1 agonist adenosine had no effect regardless of experimental approach.
Furthermore, the P2 antagonist suramin increased osmotic fragility, inhibited RVD, and reduced whole-cell conductance in swollen
cells. Consistent with a previous study that indicated cell swelling activates a K+ conductance, suramin had no effect in the presence of gramicidin (a cationophore used to maintain a high K+ permeability). We also found the P2 antagonist pyridoxal-5-phosphate-6-azophenyl-2′4-disulfonic acid (PPADS) increased osmotic
fragility; however, reactive blue 2 and the P1 antagonists caffeine and theophylline had no effect. Our results show that
extracellular ATP activated a P2 receptor in Necturus erythrocytes during hypotonic swelling, which in turn potentiated RVD by stimulating K+ efflux. Pharmacological evidence suggested the presence of a P2X receptor subtype.
Received: 6 January 2001/Revised: 17 April 2001 相似文献
13.
Molz S Decker H Dal-Cim T Cremonez C Cordova FM Leal RB Tasca CI 《Neurochemical research》2008,33(1):27-36
Glutamate excitotoxicity may culminate with neuronal and glial cell death. Glutamate induces apoptosis in vivo and in cell
cultures. However, glutamate-induced apoptosis and the signaling pathways related to glutamate-induced cell death in acute
hippocampal slices remain elusive. Hippocampal slices exposed to 1 or 10 mM glutamate for 1 h and evaluated after 6 h, showed
reduced cell viability, without altering membrane permeability. This action of glutamate was accompanied by cytochrome c release, caspase-3 activation and DNA fragmentation. Glutamate at low concentration (10 μM) induced caspase-3 activation
and DNA fragmentation, but it did not cause cytochrome c release and, it did not alter the viability of slices. Glutamate-induced impairment of hippocampal cell viability was completely
blocked by MK-801 (non-competitive antagonist of NMDA receptors) and GAMS (antagonist of KA/AMPA glutamate receptors). Regarding
intracellular signaling pathways, glutamate-induced cell death was not altered by a MEK1 inhibitor, PD98059. However, the
p38MAPK inhibitor, SB203580, prevented glutamate-induced cell damage. In the present study we have shown that glutamate induces apoptosis
in hippocampal slices and it causes an impairment of cell viability that was dependent of ionotropic and metabotropic receptors
activation and, may involve the activation of p38MAPK pathway. 相似文献
14.
Wang JQ Arora A Yang L Parelkar NK Zhang G Liu X Choe ES Mao L 《Molecular neurobiology》2005,32(3):237-249
The ionotropic α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor is densely distributed in the mammalian
brain and is primarily involved in mediating fast excitatory synaptic transmission. Recent studies in both heterologous expression
systems and cultured neurons have shown that the AMPA receptor can be phosphorylated on their subunits (GluR1, GluR2, and
GluR4). All phosphorylation sites reside at serine, threonine, or tyrosine on the intracellular C-terminal domain. Several
key protein kinases, such as protein kinase A, protein kinase C, Ca2+/calmodulin-dependent protein kinase II, and tyrosine kinases (Trks; receptor or nonreceptor family Trks) are involved in
the site-specific regulation of the AMPA receptor phosphorylation. Other glutamate receptors (N-methyl-d-aspartate receptors and metabotropic glutamate receptors) also regulate AMPA receptors through a protein phosphorylation
mechanism. Emerging evidence shows that as a rapid and short-term mechanism, the dynamic protein phosphorylation directly
modulates the electrophysiological, morphological (externalization and internalization trafficking and clustering), and biochemical
(synthesis and subunit composition) properties of the AMPA receptor, as well as protein-protein interactions between the AMPA
receptor subunits and various intracellular interacting proteins. These modulations underlie the major molecular mechanisms
that ultimately affect many forms of synaptic plasticity. 相似文献
15.
Nucleotides released upon brain injury signal to astrocytes and microglia playing an important role in astrogliosis, but the
participation of microglia in the purinergic modulation of astrogliosis is still unclear. Highly enriched astroglial cultures
and co-cultures of astrocytes and microglia were used to investigate the influence of microglia in the modulation of astroglial
proliferation mediated by nucleotides. In highly enriched astroglial cultures, adenosine-5’-triphosphate (ATP), adenosine
5’-O-(3-thio)-triphosphate (ATPγS), adenosine 5’-O-(3-thio)-diphosphate (ADPβS; 0.01–1 mM), and adenosine-5’-diphosphate (ADP; 0.1–1 mM) increased proliferation up to 382%,
an effect abolished in co-cultures containing 8% of microglia. The loss of ATP proliferative effect in co-cultures is supported
by its fast metabolism and reduced ADP accumulation, an agonist of P2Y1,12 receptors that mediate astroglial proliferation. No differences in ADPβS and ATPγS metabolism or P2Y1,12 receptors expression were found in co-cultures that could explain the loss of their proliferative effect. However, conditioned
medium from microglia cultures or co-cultures treated with ADPβS, when tested in highly enriched astroglial cultures, also
prevented ADPβS proliferative effect. None of the uracil nucleotides tested had any effect in proliferation of highly enriched
astroglial cultures, but uridine-5′-triphosphate (UTP; 0.1–1 mM) inhibited proliferation up to 66% in co-cultures, an effect
that was dependent on uridine-5’-diphosphate (UDP) accumulation, coincident with a co-localization of P2Y6 receptors in microglia and due to cell apoptosis. The results indicate that microglia control astroglial proliferation by
preventing the proliferative response to adenine nucleotides and favouring an inhibitory effect of UTP/UDP. Several microglial
P2Y receptors may be involved by inducing the release of messengers that restrain astrogliosis, a beneficial effect for neuronal
repair mechanisms following brain injury. 相似文献
16.
Arriagada C Dagnino-Subiabre A Caviedes P Armero JM Caviedes R Segura-Aguilar J 《Amino acids》2000,18(4):363-373
Summary. Aminochrome was found to be toxic in a mouse-derived neuronal cell line (CNh). The effect was concentration dependent (10–150
μM). The issue whether aminochrome toxicity involves glutamate transmission was studied with several glutamate receptors antagonists.
Incubation of the cells with aminochrome (150 μM) in the presence of 100 μM of the AMPA an-tagonist, NBQX resulted in an increase of cell survival, from 52 to 73%. However, this protective effect
did not seem to be related to activation of ionotropic glutamate receptors since incubation of CNh cells with 200 μM of glutamate resulted in only 10% decrease of cell survival. However, NBQX was found to inhibit in vitro the autoxidation process. One hundred μM AP-5 did not have any effect on aminochrome toxicity. The toxic effect of aminochrome on CNh cells seems to be dependent
of extracellular activation since addition of dicoumarol, a specific inhibitor of DT-diaphorase, did not affect that toxicity,
which can be explained perhaps by a lack of a transport system for aminochrome into the CNh cells.
Received July 28, 1999, Accepted December 6, 1999 相似文献
17.
This study was designed to explore the effect of P2X7 receptor (P2X7R) activation on the expression of p38 MAP kinase (p38 MAPK) enzyme in hippocampal slices of wild-type (WT) and P2X7R−/− mice using the Western blot technique and to clarify its role in P2X7 receptor mediated [3H]glutamate release. ATP (1 mM) and the P2X7R agonist BzATP (100 μM) significantly increased p38 MAPK phosphorylation in WT mice, and these effects were absent in the hippocampal slices of P2X7R−/− mice. Both ATP- and BzATP-induced p38 MAPK phosphorylations were sensitive to the p38 MAP kinase inhibitor, SB203580 (1 μM). ATP elicited [3H]glutamate release from hippocampal slices, which was significantly attenuated by SB203580 (1 μM) but not by the extracellular signal-regulated kinase (ERK1/2) inhibitor, PD098095 (10 μM). Consequently, we suggest that P2X7Rs and p38 MAPK are involved in the stimulatory effect of ATP on glutamate release in the hippocampal slices of WT mice. 相似文献
18.
Neuronal synchrony mediated by astrocytic glutamate through activation of extrasynaptic NMDA receptors 总被引:31,自引:0,他引:31
Fast excitatory neurotransmission is mediated by activation of synaptic ionotropic glutamate receptors. In hippocampal slices, we report that stimulation of Schaffer collaterals evokes in CA1 neurons delayed inward currents with slow kinetics, in addition to fast excitatory postsynaptic currents. Similar slow events also occur spontaneously, can still be observed when neuronal activity and synaptic glutamate release are blocked, and are found to be mediated by glutamate released from astrocytes acting preferentially on extrasynaptic NMDA receptors. The slow currents can be triggered by stimuli that evoke Ca2+ oscillations in astrocytes, including photolysis of caged Ca2+ in single astrocytes. As revealed by paired recording and Ca2+ imaging, a striking feature of this NMDA receptor response is that it occurs synchronously in multiple CA1 neurons. Our results reveal a distinct mechanism for neuronal excitation and synchrony and highlight a functional link between astrocytic glutamate and extrasynaptic NMDA receptors. 相似文献
19.
Regulation of neuronal ion channels via P2Y receptors 总被引:1,自引:0,他引:1
Within the last 15 years, at least 8 different G protein-coupled P2Y receptors have been characterized. These mediate slow metabotropic effects of nucleotides in neurons as well as non-neural cells, as opposed to the fast ionotropic effects which are mediated by P2X receptors. One class of effector systems regulated by various G protein-coupled receptors are voltage-gated and ligand-gated ion channels. This review summarizes the current knowledge about the modulation of such neuronal ion channels via P2Y receptors. The regulated proteins include voltage-gated Ca2+ and K+ channels, as well as N-methyl-d-aspartate, vanilloid, and P2X receptors, and the regulating entities include most of the known P2Y receptor subtypes. The functional consequences of the modulation of ion channels by nucleotides acting at pre- or postsynaptic P2Y receptors are changes in the strength of synaptic transmission. Accordingly, ATP and related nucleotides may act not only as fast transmitters (via P2X receptors) in the nervous system, but also as neuromodulators (via P2Y receptors). Hence, nucleotides are as universal transmitters as, for instance, acetylcholine, glutamate, or -aminobutyric acid. 相似文献
20.
Effects of bilobalide on amino acid release and electrophysiology of cortical slices 总被引:2,自引:0,他引:2
Summary. This study investigated the effects of bilobalide, a constituent of Ginkgo biloba, on potassium and veratridine-induced release of glutamate and aspartate from mouse cortical slices. We also studied its
effects on spontaneous and N-methyl-D-aspartate (NMDA)-induced depolarizations elicited in magnesium-free artificial cerebrospinal
fluid (aCSF) as well as its effect on NO-711 (a γ-aminobutyric acid (GABA) uptake inhibitor)-induced depolarizations. Bilobalide, 100 μM significantly reduced both glutamate and aspartate release elicited by potassium or veratridine. Bilobalide (5–100 μM) also significantly reduced the frequency of NO-711 induced depolarizations, however, it had no effect on spontaneous or
on NMDA-induced depolarizations at 5–200 μM. These results suggest that the neuroactive properties of bilobalide may be mediated by a reduction in excitatory amino
acid neurotransmitter release.
Received June 25, 2001 Accepted October 4, 2001 相似文献