共查询到20条相似文献,搜索用时 8 毫秒
1.
W. K. Scholz 《Journal of neurochemistry》1994,62(5):1764-1772
Abstract: Previous results showed that within 30 s after glutamate stimulation of cultured rat hippocampal pyramidal neurons there occurred an elevation of Ca2+ and diacylglycerol, and the phosphorylation of three acidic protein kinase C substrates, i.e., an 87-kDa protein known as myristoylated alanine-rich C kinase substrate and a 120-and a 48-kDa protein. In addition, it was suggested that a metabotropic-type glutamate receptor might be responsible for the phosphorylation observed. This work examines the ability of metabotropic and ionotropic glutamate receptor agonists to quickly activate phospholipases in 1.26 mM versus 50 nM extracellular Ca2+ by measuring the generation of inositol phosphates. NMDA, quisqualate, and trans-(±)-1-amino-1,3-cyclopentanedicarboxylic acid did not stimulate the generation of inositol phosphates in the presence of normal or low extracellular Ca2+ in pyramidal neurons. Kainate stimulated the production of inositol phosphates in the presence of 1.26 mM extracellular Ca2+ but not in 50 nM extracellular Ca2+. Other than glutamate, only ibotenate was able to stimulate the generation of inositol phosphates in both normal and low extracellular Ca2+. The maximal response to ibotenate was approximately equal to that of glutamate, when pyramidal neurons were stimulated in 50 nM extracellular Ca2+. The generation of inositol phosphates by glutamate and ibotenate could be partially blocked (50–60% reduction) by pretreatment of neurons with pertussis toxin (250 ng/ml),-suggesting that a GTP-binding protein might be involved. In addition, ibotenate stimulated the immediate phosphorylation of the same three protein kinase C substrates as glutamate. The NMDA receptor blocker MK-801 had no effect on this phosphorylation. These results suggest that the stimulation of phosphorylation in pyramidal neurons by glutamate occurs predominantly through the activation of an ibotenate-selective metabotropic glutamate receptor. 相似文献
2.
A detailed pharmacological characterization of metabotropic glutamate receptors (mGluR) was performed in primary cultures of cerebellar granule cells at 6 days in vitro (DIV). The rank order of agonists induced polyphosphoinositide (PPI) hydrolysis (after correcting for the ionotropic component in the response) was as follows: in terms of efficiency, Glu>quisqualate (quis)=ibotenate (ibo)>(1S,3R)-1-amino-cyclopentane-1,3-dicarboxylic acid (ACPD)>-methyl-amino-l-alanine (BMAA) and in terms of potency, quis>ACPD>Glu>ibo=BMAA. Ionotropic excitatory amino acid (EAA) receptor agonists, such as -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) were relatively inactive (in the presence of Mg2+). Quis and ACPD-induced PPI hydrolysis was unaffected by ionotropic Glu receptor antagonists, but was inhibited, in part by L-2-amino-3-phosphonopropionate (AP3). In contrast, Glu-or ibo- induced PPI hydrolysis was reduced, in part, by both AP3 and NMDA receptor antagonists. Characteristic interactions involving different transmitter receptors were noted. PPI hydrolysis evoked by quis and 1S,3R-ACPD was not additive. In contrast, PPI hydrolysis stimulated by quis/ACPD and carbamylcholine was additive (indicating different receptors/transduction pathways). In the presence of Mg2+, the metabotropic response to quis/AMPA and NMDA was synergistic (this being consistent with AMPA receptor-induced depolarization activating NMDA receptor). On the other hand, in Mg2+-free buffer the effects of quis and NMDA, at concentrations causing maximal PPI hydrolysis, were additive (indicating that PPI hydrolysis was effected by two different mechanisms). Thus, in cerebellar granule cells EAAs elicit PPI hydrolysis by acting at two distinct receptor types: (i) metabotropic Glu receptors (mGluR), with pharmacological characteristics suggesting the expression of a unique mGluR receptor that shows certain similarities to those observed for the mGluR1 subtype (Aramori and Nakanishi, 1992) and (ii) NMDA receptors. The physiological agonist, Glu, is able to stimulate both receptor classes.Abbreviations ACPD
(1S,3R)-1-amino-cyclopentane-1,3-dicarboxylic acid
- AMPA
-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid
- AP3
L-2-amino-3-phosphono-propionate
- AP5
D-2-amino-5-phosphonopentenoate
- BMAA
-methyl-amino-L-alanine
- DIV
days in vitro
- DNOX
6,7-dinitroouinoxoline-2,3-dione
- EAA
excitatory amino acids
- Glu
glutamate
- InsP
inositol monophosphate
- mGluR
metabotropic glutamate receptors
- MK-801
(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohept-5,10-imine hydrogen maleate
- NMDA
N-methyl-D-aspartate
- PPI
polyphosphoinositide
- quis
quisqualate 相似文献
3.
To examine whether multiple subtypes of the excitatory amino acid (EAA) receptor coupled to phosphoinositide (PPI) hydrolysis exist, we have pharmacologically characterized the PPI response in neonatal and adult rat brain. Activation of PPI hydrolysis was determined by the accumulation of [3H]inositol monophosphate in brain slices prelabeled with [3H]inositol. In neonatal hippocampus, D,L-2-amino-3-phosphonopropionic acid (AP3; 1 mM) inhibited the cis-1-aminocyclopentane-1,3-dicarboxylic acid (IUPAC nomenclature; ACPD; 100 microM)- and quisqualate (Quis; 100 microM)-stimulated PPI hydrolysis by 73 and 66%, respectively, but had no effect in neonatal cerebellum. In adult hippocampus, AP3 stimulated PPI hydrolysis with potency and efficacy comparable to those of Quis and ACPD and completely masked the Quis concentration-response curve. In adult cerebellum, only Quis behaved as a full agonist on the PPI response. The Quis concentration-response curve was shifted rightward with a fourfold decrease in potency in the presence of ACPD (5 mM), whereas it was nearly additive with the PPI response induced by AP3 (5 mM). Thus, our data reveal significant developmental and brain regional differences in metabotropic EAA receptor responses and support the notion that this receptor is heterogeneous, in both a regionally specific and a developmentally dependent manner. 相似文献
4.
Diptiman D. Bose 《Biochemical and biophysical research communications》2009,379(2):594-133
Regulation of bi-directional communication between intracellular Ca2+ pools and surface Ca2+ channels remains incompletely characterized. We report Ca2+ release mediated by inositol 1,4,5-trisphosphate receptor (IP3R) and ryanodine receptor (RyR) pathways is diminished under actin cytoskeleton disruption in NG115-401L (401L) neuronal cells, yet despite truncated Ca2+ release, Ca2+ influx was not significantly altered in these experiments. However, disruption of cortical actin networks completely abolished IP3R induced Ca2+ release, whereas RyR-mediated Ca2+ release was preserved, albeit attenuated. Moreover, cortical actin disruption completely abolished IP3R and RyR linked Ca2+ influx even though Ca2+ pool sensitivities were different. These findings suggest discrete Ca2+ store/Ca2+ channel coupling mechanisms in the IP3R and RyR pathways as revealed by the differential sensitivity to actin perturbation. 相似文献
5.
Regulation of nitric oxide (NO) formation is critical to ensure maintenance of appropriate cellular concentrations of this labile, signaling molecule. This study investigated the role exogenous and endogenously produced NO have in feeding back to regulate NO synthesis in intact cells. Two NO donors inhibited activation of neuronal NO synthase (nNOS) in response to the muscarinic receptor agonist carbachol in Chinese hamster ovary (CHO) cells stably transfected with the M1 muscarinic receptor and nNOS. The presence of the NO scavenger [2-(4-Carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide · potassium salt] (C-PTIO) potentiated carbachol-induced activation of nNOS in transfected CHO cells. C-PTIO also potentiated nNOS activity in response to the Ca2+ ionophore ionomycin. In contrast, the NO scavenger oxyhemoglobin depressed carbachol- and ionomycin-induced NO formation. These discrepant results suggest that it is unlikely that endogenously produced NO induces feed back inhibition at the level of nNOS activation itself. Exogenous sources of NO inhibited carbachol-induced inositol phosphates formation. However, endogenously produced NO did not appear to feed back to regulate phosphoinositide hydrolysis as there was no difference in [3H]inositol phosphates formation between cells that do or do not express nNOS. There was also no change in carbachol-induced [3H]inositol phosphates formation in the presence or absence of a NOS inhibitor or the NO scavenger C-PTIO. A decrease in the carbachol-mediated transient Ca2+ peak was observed in cells that express nNOS as compared to cells lacking the enzyme, suggesting that endogenous NO might inhibit receptor mediated Ca2+ signaling. This conclusion, however, was not supported by the lack of ability of a NOS inhibitor to modulate carbachol-induced Ca2+ elevations. Taken together, these results highlight differences in the regulation of the nNOS activation cascade by endogenous vs. exogenous sources of NO. 相似文献
6.
Pharmacological modulation of intracellular Ca2+ channels at the single-channel level 总被引:4,自引:0,他引:4
Synaptic signaling, memory formation, neuronal development, and neuronal pathology are strongly influenced by the properties
of intracellular Ca2+ channels, ryanodine, and inositol 1, 4, 5 trisphosphate receptors. This review will focus on recently developed and discovered
pharmacological tools to modulate these channel proteins at the single-channel level. It will allow the readers of Molecular Neurobiology to evaluate the current knowledge on the pharmacological modulation of intracellular Ca2+ channels and to direct future research efforts effectively using available experimental tools and concepts. 相似文献
7.
Peter B. Simpson 《Journal of bioenergetics and biomembranes》2000,32(1):5-13
Ca2+ signals propagate in wave form along individual cells of the central nervous system(CNS) and through networks of connected cells of neuronal and multiple glial cell types. Inorder for wave fronts to convey information, signaling mechanisms are required that allowwaves to propagate reproducibly and without decrement in signal strength over long distances.CNS Ca2+ waves are under specific integrated local control, made possible by interactions atlocal subcellular microdomains between endoplasmic reticulum and mitochondria. Activemitochondria located near the mouth of inositol trisphosphate receptor (InsP3R) channel clustersin glia take up Ca2+, which may prevent a buildup of Ca2+ around the InsP3R channel, therebydecreasing the rate of Ca2+-induced receptor inactivation, and prolonging channel open time.Mitochondria may amplify InsP;i3-dependent Ca2;pl signals by a transient permeability transitionin response to Ca2+ uptake into the mitochondrion. Other evidence suggests privileged accessinto mitochondria for Ca2+ entering neurons by glutamatergic receptor channels. This enablesspecific signal modulation as the Ca2+ wave is propagated into neurons, such that mitochondrialocated close to glutamate channels can prolong the neuronal cytosolic response time bysuccessive uptake and release of Ca2+. Disruption of mitochondrial function deregulates theability of CNS-derived cells to undergo normal Ca2+ signaling and wave propagation. 相似文献
8.
The cyclic nucleotide-activated conductance in olfactory cilia: Effects of cytoplasmic Mg2+ and Ca2+
Steven J. Kleene 《The Journal of membrane biology》1993,131(3):237-243
Summary Olfactory receptor neurons depolarize in response to odorants. This depolarization is mediated by an increase in intracellular cyclic AMP, which directly gates channels in the membranes of the neuronal cilia. Previous evidence suggests that a Ca2+ influx during the odorant response may ultimately play a role in terminating the response. One way Ca2+ inside the cell could terminate the odorant response would be to directly inhibit the cAMP-gated channels. In this report the effects of cytoplasmic Ca2+ and Mg2+ on the cAMP-activated current were measured in single olfactory cilia. Near the neuronal resting potential, cytoplasmic Ca2+ and Mg2+ only slightly reduced the cAMP-activated current. Even at high levels (1.0mm Ca2+ or 5.0mm Mg2+), the average inhibition was only around 20%. It is therefore unlikely that an influx of divalent cations terminates the odorant response by a direct effect on the cAMP-gated channels. 相似文献
9.
Dimitrios E. Kouzoukas Guiying Li Maysaam Takapoo Thomas Moninger Ramesh C. Bhalla Nicholas J. Pantazis 《Journal of neurochemistry》2013,124(3):323-335
Alcohol is a potent neuroteratogen that can trigger neuronal death in the developing brain. However, the mechanism underlying this alcohol‐induced neuronal death is not fully understood. Utilizing primary cultures of cerebellar granule neurons (CGN), we tested the hypothesis that the alcohol‐induced increase in intracellular calcium [Ca2+]i causes the death of CGN. Alcohol induced a dose‐dependent (200–800 mg/dL) neuronal death within 24 h. Ratiometric Ca2+ imaging with Fura‐2 revealed that alcohol causes a rapid (1–2 min), dose‐dependent increase in [Ca2+]i, which persisted for the duration of the experiment (5 or 7 min). The alcohol‐induced increase in [Ca2+]i was observed in Ca2+‐free media, suggesting intracellular Ca2+ release. Pre‐treatment of CGN cultures with an inhibitor (2‐APB) of the inositol‐triphosphate receptor (IP3R), which regulates Ca2+ release from the endoplasmic reticulum (ER), blocked both the alcohol‐induced rise in [Ca2+]i and the neuronal death caused by alcohol. Similarly, pre‐treatment with BAPTA/AM, a Ca2+‐chelator, also inhibited the alcohol‐induced surge in [Ca2+]i and prevented neuronal death. In conclusion, alcohol disrupts [Ca2+]i homeostasis in CGN by releasing Ca2+ from intracellular stores, resulting in a sustained increase in [Ca2+]i. This sustained increase in [Ca2+]i may be a key determinant in the mechanism underlying alcohol‐induced neuronal death. 相似文献
10.
《Channels (Austin, Tex.)》2013,7(3):193-202
Prolactin (PRL) activates PRL receptor isoforms to exert regulation of specific neuronal circuitries, and to control numerous physiological and clinically-relevant functions including; maternal behavior, energy balance and food intake, stress and trauma responses, anxiety, neurogenesis, migraine and pain. PRL controls these critical functions by regulating receptor potential thresholds, neuronal excitability and/or neurotransmission efficiency. PRL also influences neuronal functions via activation of certain neurons, resulting in Ca2+ influx and/or electrical firing with subsequent release of neurotransmitters. Although PRL was identified almost a century ago, very little specific information is known about how PRL regulates neuronal functions. Nevertheless, important initial steps have recently been made including the identification of PRL-induced transient signaling pathways in neurons and the modulation of neuronal transient receptor potential (TRP) and Ca2+-dependent K+ channels by PRL. In this review, we summarize current knowledge and recent progress in understanding the regulation of neuronal excitability and channels by PRL. 相似文献
11.
A model explaining quantal Ca2+ release as an intrinsic property of the inositol 1,4,5-trisphosphate (IP3) receptor has been put forward. The model is based on the hypothesis that the IP3 receptor can catalyze a transformation of the IP, molecule differing from its conventional metabolism. A simple kinetic mechanism is considered, in which IP3-induced Ca2+ channel opening is followed by the step of IP3 conversion and channel closure. Examination of the resulting mathematical model shows that it can reproduce well both partial release of stored Ca2+ and the same responsiveness to subsequent IP3 additions. On incorporation of an additional closed state of the channel, the model describes also a time-dependent channel inactivation at a high IP3 dose. Temperature sensitivity of the catalytic step accounts for the reported elimination of quantal responses and inactivation at low temperature. The transformation product is surmised to be a positional or stereo isomer of IP3. 相似文献
12.
Prolactin (PRL) activates PRL receptor isoforms to exert regulation of specific neuronal circuitries, and to control numerous physiological and clinically-relevant functions including; maternal behavior, energy balance and food intake, stress and trauma responses, anxiety, neurogenesis, migraine and pain. PRL controls these critical functions by regulating receptor potential thresholds, neuronal excitability and/or neurotransmission efficiency. PRL also influences neuronal functions via activation of certain neurons, resulting in Ca2+ influx and/or electrical firing with subsequent release of neurotransmitters. Although PRL was identified almost a century ago, very little specific information is known about how PRL regulates neuronal functions. Nevertheless, important initial steps have recently been made including the identification of PRL-induced transient signaling pathways in neurons and the modulation of neuronal transient receptor potential (TRP) and Ca2+-dependent K+ channels by PRL. In this review, we summarize current knowledge and recent progress in understanding the regulation of neuronal excitability and channels by PRL. 相似文献
13.
Bcl-2 interaction with the inositol 1,4,5-trisphosphate receptor: role in Ca(2+) signaling and disease 总被引:1,自引:0,他引:1
The Bcl-2 protein, best known for its ability to inhibit apoptosis, interacts with the inositol 1,4,5-trisphosphate receptor (IP3R) Ca2+ channel to regulate IP3-mediated Ca2+ release from the endoplasmic reticulum. This review summarizes the current state of knowledge regarding the interaction of Bcl-2, and also its homologue Bcl-xl, with the IP3R and how these interactions regulate Ca2+ signaling. The dual role of these interactions in promoting prosurvival Ca2+ signals, while at the same time inhibiting proapoptotic Ca2+ signals, is discussed. Moreover, this review will elucidate the recently recognized importance of the Bcl-2-IP3R interaction in human disease. 相似文献
14.
Intracellular calcium ([Ca2+]i) plays a pivotal role in neuronal ischemia. The aim of the present study was to investigate the routes of Ca2+ entry during non-excitotoxic oxygen and glucose deprivation (OGD) in acutely dissociated rat CA1 neurons. During OGD the fluo-3/fura red ratio reflecting [Ca2+]i increased rapidly and irreversibly. [Ca2+]i increased to the same degree in Ca2+ depleted medium, and also when both the ryanodine receptors (RyR) and the inositol 1,4,5-trisphosphate (IP3) receptors were blocked. When the endoplasmic reticulum (ER) Ca2+ stores were emptied with thapsigargin no increase in [Ca2+]i was observed independent of extracellular Ca2+. The OGD induced Ca2+ deregulation in isolated CA1 neurons is not prevented by removing Ca2+, or by blocking the IP3– or RyR receptors. However, when SERCA was blocked, no increase in [Ca2+]i was observed suggesting that SERCA dysfunction represents an important mechanism for ischemic Ca2+ overload. 相似文献
15.
Glutamate stimulated release of [3H]GABA was studied, during receptor desensitization block and its modulation by voltage gated Ca2+ channels, internal Ca2+ mobilization and GABA transport inhibitors from olfactory bulb slices. Under control conditions, glutamate and agonists induced release was strongly inhibited by Mg/0 Ca2+ Krebs and Cd2+ and partially inhibited by Ni2+ and nifedipine. Cyclothiazide, which blocks desensitization of glutamate receptors, potentiated glutamate, kainate, AMPA and quisqualate induced release. This effect was less dependent of entry of external Ca2+, but was inhibited by trifluoperazine and thapsigargin, inhibitors of Ca2+-calmodulin and endoplasmatic Ca2+ ATPase respectively. Nipecotic acid and NO-711, inhibitors of the GABA transporter, were also able to reduce cyclothiazide potentiated release induced by the 4 secretagogues. Under control conditions, glutamate stimulates the release of GABA in cooperation with VDCC. However, during receptor desensitization block, glutamate stimulated GABA release is mainly modulated through mechanisms dependent on internal Ca2+ mobilization and reversal of the GABA transporter. 相似文献
16.
Zanelli SA Numagami Y McGowan JE Mishra OP Delivoria-Papadopoulos M 《Neurochemical research》1999,24(3):437-446
Calcium influx via the NMDA receptor has been proposed as a mechanism of hypoxia-induced neuronal injury. The present study tests the hypothesis that the increase of [Ca2+]i observed under hypoxic conditions is the result of an NMDA-mediated Ca2+ influx. Changes of [Ca2+]i, measured fluorometrically with Fura-2, were followed after activation of the NMDA receptor with NMDA and glutamate, in the presence of glycine, in cortical synaptosomes prepared from six normoxic and six hypoxic guinea pig fetuses. [Ca2+]i was significantly higher in hypoxic vs normoxic synaptosomes, at baseline and in the presence of glycine as well as following activation of the NMDA receptor. Increase in [Ca2+]i was not observed in a Ca2+ free medium and was significantly decreased by MK-801 and thapsigargin. These results demonstrate that hypoxia-induced modifications of the NMDA receptor ion-channel results in increased [Ca2+]i in hypoxic vs normoxic synaptosomes. This increased accumulation may be due to an initial influx of Ca2+ via the altered NMDA receptor with subsequent release of Ca2+ from intracellular stores. Increase in intracellular calcium may initiate several pathways of free radical generation including cyclooxygenase, lipoxygenase, xanthine oxidase and nitric oxide synthase, and lead to membrane lipid peroxidation resulting in neuronal cell damage. 相似文献
17.
Robert V. Farese John L. Orchard Ronald E. Larson Mohammad A. Sabir John S. Davis 《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》1985,846(2):296-304
Rat pancreatic fragments and acinar preparations were incubated in vitro to characterize further the changes in phosphoinositide metabolism that occur during secretagogue action. Two distinct responses were discernible. The first response, most notably involving a decrease in phosphatidylinositol content, was (a) observed at lower carbachol concentrations in dose-response studies, (b) inhibited by incubation in Ca2+-free media containing 1 mM EGTA, (c) associated with increases in inositol monophosphate production, and (d) provoked by all tissue secretagogues (carbachol, cholecystokinin, secretin, insulin, dibutyryl cAMP and the ionophore A23187), regardless of whether their mechanism of action primarily involved Ca2+ mobilization or cAMP generation. This decrease in phosphatidylinositol content was at least partly due to phospholipase C (and/or D) activation, as evidenced by the increase in inositol monophosphate. The second response, most notably involving markedly increased incorporation of 32PO4 into phosphatidic acid and phosphatidylinositol, was (a) observed at higher carbachol concentrations, (b) not influenced by incubation in Ca2+-free media containing 1 mM EGTA, and (c) associated with increases in inositol triphosphate production. This 32PO4 turnover response was probably largely the result of phospholipase C-mediated hydrolysis of phosphatidylinositol 4′,5′-diphosphate, which, as shown previously, also occurs at higher carbachol concentrations and is insensitive to comparable EGTA-induced Ca2+ deficiency. This phosphatidylinositol 4′,5′-diphosphate hydrolysis response was only observed in the action of agents (carbachol and cholecystokinin) which mobilize Ca2+ via activation of cell surface receptors. The present results indicate that phosphatidylinositol and phosphatidylinositol 4′,5′-diphosphate hydrolysis are truly separable responses to secretagogues acting in the rat pancreas. Furthermore, phosphatidylinositol 4′,5′-diphosphate, rather than phosphatidylinositol hydrolysis is more likely to be associated with receptor activation and Ca2+ mobilization. 相似文献
18.
Yang CM Hsu MC Ong R Hsieh JT Tsao HL Chen YC Luo SF 《Journal of biomedical science》1995,2(3):283-292
Regulation of the increases in inositol 1,4,5-trisphosphate (IP3) production and intracellular Ca2+ concentration ([Ca2+]i) by activation of protein kinase C (PKC) was investigated in cultured canine tracheal smooth muscle cells (TSMCs). Stimulation of TSMCs by carbachol led to IP3 formation and caused an initial transient peak of [Ca2+]i followed by a sustained elevation in a concentration-dependent manner. Pretreatment of TSMCs with phorbol 12-myristate 13-acetate (PMA, 1 µM) for 30 min blocked the carbachol-induced IP3 formation and Ca2+ mobilization. Following preincubation, carbachol-induced Ca2+ mobilization recovered within 24 h. The concentrations of PMA that gave half-maximal inhibition of carbachol-induced IP3 formation and increase in [Ca2+]i were 7 and 4 nM, respectively. Prior treatment of TSMCs with staurosporine (1 µM), a PKC inhibitor, inhibited the ability of PMA to attenuate carbachol-induced responses. Inactive phorbol ester, 4-phorbol 12,13-didecanoate at 1 µM, did not inhibit these responses to carbachol. The Kd and Bmax of the muscarinic receptor for [3H]N-methylscopolamine binding were not significantly changed by PMA treatment. PMA also decreased PKC activity in the cytosol of TSMCs, while increasing it transiently in the membranes within 30 min. Thereafter, the membrane-associated PKC activity decreased and persisted for at least 24 h of PMA treatment. Taken together, these results suggest that activation of PKC may inhibit phosphoinositide hydrolysis and consequently attenuate the [Ca2+]i increase or inhibit both responses independently. The inhibition by PMA of carbachol-induced responses was inversely correlated with membranous PKC activity. 相似文献
19.
《Seminars in cell biology》1994,5(4):273-281
The Molecular, structural and functional characteristics of the intracellular Ca2+ release channel activated by inositol 1,4,5-trisphosphate (IP3), also named IP3 receptor (IP3R), are described here. We also discuss the differences in primary structure, expression and modulation of the receptor subtypes and their physiological roles. The similarity and differences between the IP3R and the other intracellular Ca2+ channel, the ryanodine receptor, are briefly presented. 相似文献
20.
V. Varga R. Janáky I. Holopainen P. Saransaari S. S. Oja 《Neurochemical research》1992,17(12):1195-1200
The effects of Mg2+ on the glutamate-, kainate-, N-methyl-d-aspartate- and quisqualate-induced influx of45Ca2+ were studied in cultured cerebellar granule cells. The N-methyl-d-aspartate- and quisqualate-evoked influx was totally and the kainate- and glutamate-evoked influx partially blocked in 1.3 mM extracellular Mg2+. The increase in influx induced by kainate, quisqualate and glutamate was maximal at 0.1 mM Mg2+, whereas N-methyl-d-aspartate was most effective in totally Mg2+-free media.d-2-Amino-5-phosphonovalerate blocked partially and phencyclidine completely the enhancement of Ca2+ influx by 1 mM quisqualate in 0.1-mM Mg2+ medium. The effect of 10 M quisqualate was also significantly inhibited by antagonists specific for different glutamate receptor subtypes, including N-methyl-d-aspartate, (RS)-amino-3-hydroxy-5-methyl-4-isozazolepropionate and metabotropic recptors. This evidences a heterogeneous action of quisqualate, mediated by different glutamate receptor subtypes in 0.1 mM Mg2+ medium. The efficacy of quisqualate in inducing influx of Ca+ and the selectivity of antagonists for different receptors are also modified by extracellular Mg2+. 相似文献