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1.
Effects of the kampo medicine yokukansan on gene expression of the cystine/glutamate antiporter system Xc −, which protects against glutamate-induced cytotoxicity, were examined in Pheochromocytoma cells (PC12 cells). Yokukansan inhibited glutamate-induced PC12 cell death. Similar cytoprotective effects were found in Uncaria hook. Experiments to clarify the active compounds revealed that geissoschizine methyl ether, hirsuteine, hirsutine, and procyanidin B1 in Uncaria hook, had cytoprotective effects. These components enhanced gene expressions of system Xc − subunits xCT and 4F2hc, and also ameliorated the glutamate-induced decrease in glutathione levels. These results suggest that the cytoprotective effect of yokukansan may be attributed to geissoschizine methyl ether, hirsuteine, hirsutine, and procyanidin B1 in Uncaria hook. 相似文献
2.
Geissoschizine methyl ether (GM) in Uncaria hook, a galenical constituent of yokukansan is thought to be one of active components
in the psychotropic effect of yokukansan, a traditional Japanese medicine ( kampo medicine). However, there is no data on the blood–brain barrier (BBB) permeability of Uncaria hook-derived alkaloids containing
GM. In this study, we investigated the BBB permeability of seven Uncaria hook alkaloids (GM, isocorynoxeine, isorhynchophylline,
hirsuteine, hirsutine, rhynchophylline, and corynoxeine) using in vivo and in vitro methods. In the in vivo experiment, seven
alkaloids in the plasma and brain of rats orally administered with yokukansan were measured by liquid chromatography–mass
spectroscopy/mass spectrometric multiple reaction monitoring assay. In the in vitro experiment, the BBB permeability of seven
alkaloids were examined using the BBB model composed of co-culture of endothelial cells, pericytes, and astrocytes. In the
in vivo study, six components containing GM but not isocorynoxeine were detected in the plasma, and three (GM, hirsuteine,
and corynoxeine) of components were detected in the brain. The in vitro BBB permeability data indicated that seven alkaloids
were able to cross brain endothelial cells in culture conditions and that the BBB permeability of GM was higher than those
of the other six alkaloids. These results suggest that target ingredient GM in yokukansan administered orally is absorbed
into the blood and then reaches the brain through the BBB. This evidence further supports the possibility that GM is an active
component in the psychotropic effect of yokukansan. 相似文献
3.
Effects of seven alkaloids, geissoschizine methyl ether (GM), hirsutine, hirsuteine, rhynchophylline, isorhynchophylline, corynoxeine and isocorynoxeine, in Uncaria hook, a constituent of the kampo medicine yokukansan, on serotonin 7 (5-HT 7) receptor were investigated using Chinese hamster ovary (CHO) cell membranes and human embryonic kidney 293 (HEK293) cells stably expressing the human recombinant 5-HT 7 receptor. A competitive binding assay using CHO membranes showed that GM (IC 50 = 0.034 μM) more strongly inhibited the binding of the radioligand [ 3H] LSD to 5-HT 7 receptor than the other alkaloids, suggesting that GM is bound to 5-HT 7 receptor. Agonistic/antagonistic effects of GM (1–50 μM) on the receptor were evaluated by measuring intracellular cAMP levels in HEK239 cells. GM (IC 50 = 6.0 μM) inhibited 5-HT-induced cAMP production in a concentration-dependent manner, as well as the specific 5-HT 7 receptor antagonist SB-269970 (0.1–1 μM). However, GM did not induce intracellular cAMP production as 5-HT did. These results suggest that GM has an antagonistic effect on 5-HT 7 receptor. 相似文献
4.
We have screened new drugs with a view to developing effective drugs against glutamate-induced excitotoxicity. In the present
work, we show effects of a new drug, 2-cyclopropylimino-3-methyl-1,3-thiazoline hydrochloride against glutamate-induced excitotoxicity
in primary rat glial cultures. Pretreatment of glial cells with 2-cyclopropylimino-3-methyl-1,3-thiazoline hydrochloride for
2 h significantly protected glial cells against glutamate-induced excitotoxicity in a time- and dose-dependent manner with
an optimum concentration of 100 μM. The drug significantly reduced production of proinflammatory cytokines, tumor necrosis
factor-α, and interlukin-1β in glutamate-induced excitotoxicity. The drug also prevented glutamate-induced intracellular Ca 2+ influx and reduced the subsequent overproduction of nitric oxide and reactive oxygen species. Furthermore, the drug preserved
the mitochondrial potential and inhibited the overproduction of cytochrome c. In addition, the drug effectively attenuated the protein level changes of β-catenin and glycogen synthase kinase-3β. These
results suggest that 2-cyclopropylimino-3-methyl-1,3-thiazoline hydrochloride effectively protected primary cultures of rat
glial cells against glutamate-induced excitotoxicity. 相似文献
6.
In acute and chronic neurodegeneration, Ca 2+ mishandling and disruption of the cytoskeleton compromise neuronal integrity, yet abnormalities in the signaling roles of cytoskeletal proteins remain largely unexplored. We now report that the microtubule-associated protein p600 (also known as UBR4) promotes neuronal survival. Following depletion of p600, glutamate-induced Ca 2+ influx through NMDA receptors, but not AMPA receptors, initiates a degenerative process characterized by endoplasmic reticulum fragmentation and endoplasmic reticulum Ca 2+ release via inositol 1,4,5-trisphosphate receptors. Downstream of NMDA receptors, p600 associates with the calmodulin·calmodulin-dependent protein kinase IIα complex. A direct and atypical p600/calmodulin interaction is required for neuronal survival. Thus, p600 counteracts specific Ca 2+-induced death pathways through regulation of Ca 2+ homeostasis and signaling. 相似文献
7.
The function of the GABA A receptor has been studied using the whole cell voltage clamp recording technique in rat cerebellum granule cells in culture.
Activation of NMDA-type glutamate receptors causes a reduction in the effect of GABA. Full GABA A receptor activity was recovered after washing out NMDA and NMDA action was prevented in a Mg ++ containing medium. The NMDA effect was also absent when extracellular Ca ++ was replaced by Ba ++ and when 10 mM Bapta was present in the intracellular solution. Charge accumulations via voltage activated Ca ++ channels greater than the ones via NMDA receptors do not cause any reduction in GABA A receptor function, suggesting that Ca ++ influx through NMDA receptor channels is critical for the effect. The NMDA effect was reduced by including adenosine-5′-O-3-thiophosphate
(ATP- γ-S) in the internal solution and there was a reduction in the NMDA effect caused by deltamethrin, a calcineurin inhibitor.
Part of the NMDA induced GABA A receptor impairment was prevented by prior treatment with L-arginine. Analogously, part of the NMDA effect was prevented
by blockage of NO-synthase activity by N
ω
-nitro-L-arginine. A combination of NO-synthase and calcineurin inhibitors completely eliminated the NMDA action. An analogous
result was obtained by combining the NO-synthase inhibitor with the addition of ATP- γ-S to the pipette medium. The additivity of the prevention of the NMDA impairment of GABA A receptor by blocking the L-arginine/NO pathway and inhibiting calcineurin activity suggests an independent involvement of
these two pathways in the interaction between NMDA and the GABA A receptor. On the one hand Ca ++ influx across NMDA channels activates calcineurin and dephosphorylates the GABA A receptor complex directly or dephosphorylates proteins critical for the function of the receptor. On the other hand, Ca ++ influx activates NO-synthase and induces nitric oxide production, which regulates such receptors via protein kinase G activity.
Received: 22 July 1996 / Accepted: 29 October 1996 相似文献
8.
It was established in experiments on murine hippocampal slices that low-frequency (1 sec −1, 15 min) stimulation of the Schaffer collaterals applied 45 to 60 min after their high-frequency repetitive stimulation (60
sec −1, 0.5 sec) results, in 2/3 of the slices, in reduction of the amplitude of population EPSP recorded from pyramidal neurons
of the CA1 area, almost to its level before high-frequency stimulation. Depotentiation was practically completely prevented by application
of a non-competitive blocker of NMDA glutamate receptors (GR), ketamine (100 μM), was weakened by a blocker of voltage-dependent
L-type Ca 2+ channels, nifedipine (10 μM), and remained significant after a competitive blocker of the AMPA/kainate receptors, CNQX (10
μM), had been applied to the slices. Depotentiation was significantly reduced by 10 μM of a calmodulin inhibitor, trifluoroperazine,
by an increase in the intracellular cAMP concentration caused by activation of A2-adenosine receptors and D5-dopamine receptors,
but was resistant to the action of 50 μM of a protein kinase C (PKC) inhibitor, polymixin B. Nootropic compounds possessing
anti-amnestic activity enhanced the depotentiation. It is suggested that depotentiation is due to an increase in the intracellular
Ca 2+ concentration, activation of protein phosphatases, and dephosphorylation of pre- and post-synaptic substrates involved in
the expression of long-term post-tetanic potentiation of synaptic transmission, which result from cooperative activation of
NMDA GR and metabotropic GR. 相似文献
9.
Neuronal ion channels of different types often do not function independently but will inhibit or potentiate the activity of
other types of channels, a process called cross-talk. The N-methyl- D-aspartate receptor (NMDA receptor) and the γ-aminobutyric acid type A receptor (GABA A receptor) are important excitatory and inhibitory receptors in the central nervous system, respectively. Currently, cross-talk
between the NMDA receptor and the GABA A receptor, particularly in the central auditory system, is not well understood. In the present study, we investigated functional
interactions between the NMDA receptor and the GABA A receptor using whole-cell patch-clamp techniques in cultured neurons from the inferior colliculus, which is an important
nucleus in the central auditory system. We found that the currents induced by aspartate at 100 μmol L −1 were suppressed by the pre-perfusion of GABA at 100 μmol L −1, indicating cross-inhibition of NMDA receptors by activation of GABA A receptors. Moreover, we found that the currents induced by GABA at 100 μmol L −1 ( I
GABA) were not suppressed by the pre-perfusion of 100 μmol L −1 aspartate, but those induced by GABA at 3 μmol L −1 were suppressed, indicating concentration-dependent cross-inhibition of GABA A receptors by activation of NMDA receptors. In addition, inhibition of IGABA by aspartate was not affected by blockade of voltage-dependent Ca 2+ channels with CdCl 2 in a solution that contained Ca 2+, however, CdCl 2 effectively attenuated the inhibition of I
GABA by aspartate when it was perfused in a solution that contained Ba 2+ instead of Ca 2+ or a solution that contained Ca 2+ and 10 mmol L −1 BAPTA, a membrane-permeable Ca 2+ chelator, suggesting that this inhibition is mediated by Ca 2+ influx through NMDA receptors, rather than voltage-dependent Ca 2+ channels. Finally, KN-62, a potent inhibitor of Ca 2+/calmodulin-dependent protein kinase II (CaMKII), reduced the inhibition of I
GABA by aspartate, indicating the involvement of CaMKII in this cross-inhibition. Our study demonstrates a functional interaction
between NMDA and GABA A receptors in the inferior colliculus of rats. The presence of cross-talk between these receptors suggests that the mechanisms
underlying information processing in the central auditory system may be more complex than previously believed. 相似文献
10.
Glutamate-induced elevation in intracellular Ca 2+ has been implicated in excitotoxic cell death. Neurons respond to increased glutamate levels by activating an extracellular proteolytic cascade involving the components of the plasmin-plasminogen system. AnxA2 is a Ca 2+-dependent phospholipid binding protein and serves as an extracellular proteolytic center by recruiting the tissue plasminogen activator and plasminogen and mediating the localized generation of plasmin. Ratiometric Ca 2+ imaging and time-lapse confocal microscopy demonstrated glutamate-induced Ca 2+ influx. We showed that glutamate translocated both endogenous and AnxA2-GFP to the cell surface in a process dependent on the activity of the NMDA receptor. Glutamate-induced translocation of AnxA2 is dependent on the phosphorylation of tyrosine 23 at the N terminus, and mutation of tyrosine 23 to a non-phosphomimetic variant inhibits the translocation process. The cell surface-translocated AnxA2 forms an active plasmin-generating complex, and this activity can be neutralized by a hexapeptide directed against the N terminus. These results suggest an involvement of AnxA2 in potentiating glutamate-induced cell death processes. 相似文献
11.
The basic mechanisms of regulation of Ca 2+ influx have been studied in murine myoblasts proliferating and differentiating in culture. The presence of L-type Ca 2+ channels in proliferating myoblasts is shown for the first time. It is also shown that the influx of Ca 2+ through these channels is regulated by the adrenergic system. The influx of Ca 2+ after activation of the adrenergic system by addition of adrenaline has been estimated in comparison with the contribution
of reticular stocks exhausted by ATP in calcium-free medium. The Ca 2+ influx in proliferating myoblasts is regulated by β-2 adrenergic receptors whose action is mediated by adenylate cyclase
through L-type calcium channels. In differentiating myoblasts, the adrenaline-induced Ca 2+ influx is substantially lower than in proliferating cells, and maximal influx of Ca 2+ may be reached only upon exhaustion of reticular stocks. 相似文献
12.
Metabotropic GABA B receptors are abundantly expressed at glutamatergic synapses where they control excitability of the synapse. Here, we tested the hypothesis that glutamatergic neurotransmission may regulate GABA B receptors. We found that application of glutamate to cultured cortical neurons led to rapid down-regulation of GABA B receptors via lysosomal degradation. This effect was mimicked by selective activation of AMPA receptors and further accelerated by coactivation of group I metabotropic glutamate receptors. Inhibition of NMDA receptors, blockade of L-type Ca 2+ channels, and removal of extracellular Ca 2+ prevented glutamate-induced down-regulation of GABA B receptors, indicating that Ca 2+ influx plays a critical role. We further established that glutamate-induced down-regulation depends on the internalization of GABA B receptors. Glutamate did not affect the rate of GABA B receptor endocytosis but led to reduced recycling of the receptors back to the plasma membrane. Blockade of lysosomal activity rescued receptor recycling, indicating that glutamate redirects GABA B receptors from the recycling to the degradation pathway. In conclusion, the data indicate that sustained activation of AMPA receptors down-regulates GABA B receptors by sorting endocytosed GABA B receptors preferentially to lysosomes for degradation on the expense of recycling. This mechanism may relieve glutamatergic synapses from GABA B receptor-mediated inhibition resulting in increased synaptic excitability. 相似文献
13.
Steroid hormones, beside their classical genomic mechanism of action, exert rapid, non genomic effects in different cell types.
These effects are mediated by still poorly characterized plasma membrane receptors that appear to be distinct from the classic
intracellular receptors. In the present study we evaluated the non genomic effects of estradiol (17βE 2) in human sperm and its effects on sperm stimulation by extracellular ATP, a potent activator of sperm acrosome reaction.
In human sperm 17βE 2 induced a rapid increase of intracellular calcium (Ca 2+) concentrations dependent on an influx of Ca 2+ from the extracellular medium. The monitoring of the plasma membrane potential variations induced by 17βE 2 showed that this steroid induces a rapid plasma membrane hyperpolarization that was dependent on the presence of Ca 2+ in the extracellular medium since it was absent in Ca 2+ free-medium. When sperm were pre-incubated in the presence of the K + channel inhibitor tetra-ethylammonium, the 17βE 2 induced plasma membrane hyperpolarization was blunted suggesting the involvement of K + channels in the hyperpolarizing effects of 17βE 2. Extracellular ATP induced a rapid plasma membrane depolarization followed by acrosome reaction. Sperm pre-incubation with
17βE 2 inhibited the effects of extracellular ATP on sperm plasma membrane potential variations and acrosome reaction. The effects
of 17βE 2 were specific since its inactive steroisomer 17αE 2 was inactive. Furthermore the effects of 17βE 2 were not inhibited by tamoxifen, an antagonist of the classic 17βE 2 intracellular receptor. 相似文献
14.
The accumulation of glutamate can excessively activate the N-methyl- d-aspartate (NMDA) receptors and cause excitotoxicity. Vitexin (5, 7, 4-trihydroxyflavone-8-glucoside, Vit) is a c-glycosylated flavone which was found in the several herbs, exhibiting potent hypotensive, anti-inflammatory, and neuroprotective properties. However, little is known about the neuroprotective effects of Vit on glutamate-induced excitotoxicity. In present study, primary cultured cortical neurons were treated with NMDA to induce the excitotoxicity. Pretreatment with Vit significantly prevented NMDA-induced neuronal cell loss and reduced the number of apoptotic neurons. Vit significantly inhibited the neuronal apoptosis induced by NMDA exposure by regulating balance of Bcl-2 and Bax expression and the cleavages of poly (ADP-ribose) polymerase and pro-caspase 3. Furthermore, pretreatment of Vit reversed the up-regulation of NR2B-containing NMDA receptors and the intracellular Ca 2+ overload induced by NMDA exposure. The neuroprotective effects of Vit are related to inhibiting the activities of NR2B-containing NMDA receptors and reducing the calcium influx in cultured cortical neurons. 相似文献
15.
Sodium (Na +) is the major cation in extracellular space and, with its entry into cells, may act as a critical intracellular second messenger
that regulates many cellular functions. Through our investigations of mechanisms underlying the activity-dependent regulation
of N-methyl- d-aspartate (NMDA) receptors, we recently characterized intracellular Na + as a possible signaling factor common to processes underlying the upregulation of NMDA receptors by non-NMDA glutamate channels,
voltage-gated Na + channels, and remote NMDA receptors. Furthermore, although Ca 2+ influx during the activation of NMDA receptors acts as a negative feedback mechanism that downregulates NMDA receptor activity,
Na + influx provides an essential positive feedback mechanism to overcome Ca 2+-induced inhibition, thereby potentiating both NMDA receptor activity and inward Ca 2+ flow. NMDA receptors may be recruited to cause excitoxicity through a Na +-dependent mechanism. Therefore, the further characterization of mechanisms underlying the regulation of NMDA receptors by
intracellular Na + is essential to understanding activity-dependent neuroplasticity in the nervous system. 相似文献
16.
We studied the release of [ 3H] d-aspartate evoked by glutamate receptor agonists from monolayer cultures of chick retina cells, and found that activation
of the glutamate receptors can evoke both Ca 2+-dependent and Ca 2+-independent release of [ 3H] d-aspartate. In Ca 2+-free (no added Ca 2+) Na + medium, the agonists of the glutamate receptors induced the release of [ 3H] d-aspartate with the following rank order of potency: kainate>α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)∼N-methyl- d-aspartate (NMDA). In media containing 1 mM CaCl 2 the release of [ 3H] d-aspartate evoked by NMDA, kainate and AMPA was increased by about 112%, 20% and 39%, respectively, as compared to the release
evoked by the same agonists in Ca 2+-free medium. NMDA was the most potent agonist in stimulating the Ca 2+-dependent release of [ 3H] d-aspartate, possibly by exocytosis, and AMPA was as potent as kainate. The Ca 2+-dependent release of [ 3H] d-aspartate evoked by kainate was dependent on the influx of Ca 2+ through the receptor associated channel, as well as through the N- (ω-Conotoxin GVIA-sensitive) and L- (nitrendipine-sensitive)type
voltage-sensitive Ca 2+ channels (VSCC). The exocytotic release of [ 3H] d-aspartate evoked by AMPA relied exclusively on Ca 2+ entry through the L-type VSCC, whereas the effect of NMDA was partially mediated by the influx of Ca 2+ through the receptor-associated channel, but not through L- or N-type VSCC. Thus, activation of these different glutamate
receptors under physiological conditions is expected to cause the release of cytosolic and vesicular glutamate, and the routes
of Ca 2+ entry modulating vesicular release may be selectively recruited. 相似文献
17.
BackgroundHyperexcitability of neuronal networks can lead to excessive release of the excitatory neurotransmitter glutamate, which in turn can cause neuronal damage by overactivating NMDA-type glutamate receptors and related signaling pathways. This process (excitotoxicity) has been implicated in the pathogenesis of many neurological conditions, ranging from childhood epilepsies to stroke and neurodegenerative disorders such as Alzheimer’s disease (AD). Reducing neuronal levels of the microtubule-associated protein tau counteracts network hyperexcitability of diverse causes, but whether this strategy can also diminish downstream excitotoxicity is less clear. MethodsWe established a cell-based assay to quantify excitotoxicity in primary cultures of mouse hippocampal neurons and investigated the role of tau in exicitotoxicity by modulating neuronal tau expression through genetic ablation or transduction with lentiviral vectors expressing anti-tau shRNA or constructs encoding wildtype versus mutant mouse tau. ResultsWe demonstrate that shRNA-mediated knockdown of tau reduces glutamate-induced, NMDA receptor-dependent Ca2+ influx and neurotoxicity in neurons from wildtype mice. Conversely, expression of wildtype mouse tau enhances Ca2+ influx and excitotoxicity in tau-deficient (Mapt
−/−) neurons. Reconstituting tau expression in Mapt
−/− neurons with mutant forms of tau reveals that the tau-related enhancement of Ca2+ influx and excitotoxicity depend on the phosphorylation of tau at tyrosine 18 (pY18), which is mediated by the tyrosine kinase Fyn. These effects are most evident at pathologically elevated concentrations of glutamate, do not involve GluN2B–containing NMDA receptors, and do not require binding of Fyn to tau’s major interacting PxxP motif or of tau to microtubules. ConclusionsAlthough tau has been implicated in diverse neurological diseases, its most pathogenic forms remain to be defined. Our study suggests that reducing the formation or level of pY18-tau can counteract excitotoxicity by diminishing NMDA receptor-dependent Ca2+ influx. 相似文献
18.
3- Iso-19- epi-ajmalicine, epiallo-corynantheine and dihydrocorynantheine pseudoindoxyl, not previously known as natural products, have been isolated from samples of U. attenuata. Akuammigine, dihydrocorynantheine, hirsutine, hirsuteine, mitraphylline, speciophylline, uncarines A and B, isorhynchophylline rhynchophylline, isocorynoxeine, corynoxeine, corynoxine B, rotundifoline, speciofoline, two yohimbine isomers, a yohimbine oxindole and an unidentified indole alkaloid (M +, m/e 347) have been obtained from samples of the same species. 3- Iso-ajmalicine, harmane, isopteropodine, pteropodine, uncarine F, speciophylline, isomitraphylline, mitraphylline and N-oxides of these six oxindole alkaloids have been isolated from samples of U. orientalis. Several samples of U. canescens have yielded harmane while one sample contained the four pteropodine isomers. The variation in the alkaloid content of these three species is discussed. 相似文献
19.
The effect of β-endorphin on 2-, 4-, and 8-cell embryo development in vitro was studied. It is shown that the hormone has
no effect on a 2-cell embryo development, but it has enhanced viability of 4- and 8-cell mouse embryos. The number of blastocyst
formations increases in the presence of 0.1 μM β-endorphin in embryo cultured medium, and the number of blastocysts with abnormal
structure decreases. The effect of the hormone on the change of intracellular concentration of Ca 2+ ions in 2-, 4-, and 8-cell mouse embryos has been studied with the help of fluorescent microscopy. The effect of adenylate
cyclase and phospholipase activity blockers, and naloxone on the change of intracellular concentration of Ca 2+ ions in the early mouse embryo in the presence of β-endorphin has also been studied. It is shown that 2-cell embryos have
opioid and nonopioid β-endorphin receptors, whereas 4- and 8-cell mouse embryos have only nonopioid β-endorphin receptors.
It is also shown that the effect of β-endorphin in the early mouse embryo through nonopioid receptors occurs with the participation
of intracellular Ca 2+ and adenylate cyclase signaling system. 相似文献
20.
β-Amyloid, a 39–43 amino acid peptide, may exert its biological effects via neuronal nicotinic acetylcholine receptors. Using
the ratiometric dye, fura-2, we examined the effect of soluble β-amyloid 1–42 on the concentration of intracellular Ca 2+ ([Ca 2+] i) in acutely dissociated rat basal forebrain neurons. Focal applications of nicotine (0.5–20 mM), evoked dose-dependent increases
in intracellular [Ca 2+] i that were mediated by the entry of extracellular Ca 2+ via nicotinic acetylcholine receptors, and the release of intracellular Ca 2+ from stores. With repeated nicotine challenges, the nicotinic responses were potentiated by 98 ± 12% ( P < 0.05) while β-amyloid 1–42 (100 nM) was present for ∼5 min. This potentiation became larger during the subsequent washout of β-amyloid 1–42, which was associated with a gradual rise in baseline [Ca 2+] i. Application of β-amyloid 1–42 by itself did not alter [Ca 2+] i, and β-amyloid 1–42 also had no significant effect on the response to repeated KCl challenges. Therefore, β-amyloid 1–42 caused neither gross disturbance of cellular Ca 2+ homeostasis nor enhancement of voltage-gated Ca 2+ channels. Interestingly, β-amyloid 1–42 transiently potentiated the response to repeated caffeine challenges, which was also associated with a transient rise in
baseline [Ca 2+] i. β-amyloid 1–42 potentiation of nicotine-evoked rises in [Ca 2+] i was reversed by the SERCA pump inhibitor, thapsigargin, and the mitochondrial Na +/Ca 2+ exchanger inhibitor, CGP-37157. These results suggest that the dysregulation of [Ca 2+] i by β-amyloid 1–42 during multiple challenges with nicotine or caffeine involved the sensitization or overfilling of intracellular stores that
are maintained by SERCA pump and Ca 2+ efflux from the mitochondria. 相似文献
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