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1.
Effect of inositol 1,4,5-trisphosphate and GTP on calcium release from pituitary microsomes 总被引:2,自引:0,他引:2
Microsomal vesicles from bovine anterior pituitary accumulate Ca2+ and maintain a steady-state ambient Ca2+ level of 200 nM. IP3 and GTP both induce calcium release from the microsomal vesicles. The effect of IP3 is inhibited by polyethylene glycol (PEG), and the effect of GTP is absolutely dependent on PEG. Half-maximal effect of IP3 (without PEG) is 0.26 micron, the maximal calcium release attaining 7% of the A23187-releasable pool. The same values for GTP (in the presence of PEG) are 80 microM and 10%, respectively. GTP potentiates the effect of IP3. This potentiation is not mediated by protein phosphorylation. 相似文献
2.
Auranofin, an antiarthritic gold compound, modulates a number of chemotactic factor-induced inflammatory responses in human neutrophils. In order to unravel the mechanism involved, the present study investigated the effects of auranofin on early signal transduction events in these cells. Auranofin did not affect the chemotactic peptide (fMetLeuPhe)-induced formation of inositol 1,4,5-trisphosphate (Ins(1,4,5)P3), neither in the presence nor in the absence of extracellular calcium ions. In contrast, there was a progressive inhibition by auranofin on the fMet-Leu-Phe-induced mobilization of intracellular calcium. This demonstrates that auranofin can dissociate the generation of Ins(1,4,5)P3 from the subsequent release of intracellular calcium, perhaps by interfering with the intracellular binding of Ins(1,4,5)P3 to its receptor. In experiments performed in electro-permeabilized cells, however, a relatively high concentration of the drug failed to abolish the specific binding of Ins(1,4,5)P3. In addition, in the same system, auranofin also failed to abolish the Ins(1,4,5)P3-induced release of Ca2+. Consequently, auranofin-mediated dissociation of fMLP-induced Ins(1,4,5)P3 formation and intracellular calcium release can not be explained merely by an antagonistic effect of auranofin on the Ins(1,4,5)P3 receptor. Instead the interaction between auranofin and the plasma membrane seems to be an initial and important part of the mechanism by which this drug interferes with the transduction signalling system. 相似文献
3.
Several studies have indicated the existence of direct effects of melatonin on platelets. Here we show that, melatonin at high concentration is capable of significantly raising platelet intracellular calcium even in the absence of an agonist. The effect of melatonin on platelets was abolished by luzindole, a melatonin receptor blocker, and rotenone, while it was unaffected by cell-permeable antagonists of either inositol 1,4,5-trisphosphate (IP(3)) receptor, phospholipase C (PLC), or bafilomycin A1, which discharges acidic calcium stores. Melatonin-induced manganese entry provided evidence for activation of bivalent cation entry. Thus, our data suggest that melatonin evoked the elevation of platelet intracellular calcium through depletion of mitochondrial Ca(2+) stores and store-operated calcium entry (SOCE), while the action was independent of the PLC-IP(3) axis. 相似文献
4.
Our previous studies have demonstrated that calmodulin binds to IP3R type I (IP3R1) in a Ca2+ dependent manner, which suggests that calmodulin regulates the IP3R1 channel. In the present study, we investigated real-time kinetics of interactions between calmodulin and IP3R1 as well as effects of calmodulin on IP3-induced Ca2+ release by purified and reconstituted IP3R1. Kinetic analysis revealed that calmodulin binds to IP3R1 in a Ca2+ dependent manner and that both association and dissociation phase consist of two components with time constants of k(a) = 4.46 x 10(2) and > 10(4) M(-1) s(-1) k(d) = 1.44 x 10(-2) and 1.17 x 10(-1) s(-1). The apparent dissociation constant was calculated to be 27.3 microM. The IP3-induced Ca2+ release through the purified and reconstituted IP3R1 was inhibited by Ca2+/calmodulin, in a dose dependent manner. We interpret our findings to mean that calmodulin binds to IP3R1 in a Ca2+ dependent manner to exert inhibitory effect on IP3R channel activity. This event may be one of the mechanisms governing the negative feedback regulation of IP3-induced Ca2+ release by Ca2+. 相似文献
5.
Kinetics of intracellular calcium release by inositol 1,4,5-trisphosphate and extracellular ATP in porcine cultured aortic endothelial cells. 总被引:3,自引:0,他引:3
Quantitative, time-resolved measurements have been made of intracellular Ca ion release by inositol 1,4,5-trisphosphate (InsP3) and extracellular ATP in porcine aortic endothelial cells in tissue culture. Intracellular free [Ca] was detected with the calcium dye fluo-3 and InsP3 released intracellularly by photolysis of 'caged' InsP3 in whole-cell voltage-clamped aortic endothelial cells. A rise of [Ca] was recorded at InsP3 concentrations greater than 0.2 microM. The timecourse at low InsP3 concentrations comprised a delay of mean 300 ms (range 266-330 ms), a peak in 2-3 s before declining with a half-time of 5-10 s. The delay and time-to-peak decreased with increasing concentrations of InsP3 over the range 0.2-5 microM. At very high concentrations of InsP3 (> 5 microM), the delay in the Ca response was short, always less than 20 ms. The results are consistent with a direct binding and gating action of InsP3 on the Ca channel of the cellular store. Following InsP3 action there is a refractoriness of the InsP3 Ca release process which recovers with a timecourse of half-time about 30 s. A comparison can be made between the timecourse of InsP3 and extracellular ATP actions. High concentrations of ATP (500 microM) acted with a delay of mean 1.8 s (range 1.2-2.5 s), whereas even moderate concentrations of InsP3 acted much more quickly, suggesting that there are slow coupling steps before or during the production of InsP3 in response to extracellular ATP. Both ATP and InsP3 evoked an increase in membrane conductance to K+, probably via Ca. 相似文献
6.
Cytosolic inositol 1,4,5-trisphosphate dynamics during intracellular calcium oscillations in living cells
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Matsu-ura T Michikawa T Inoue T Miyawaki A Yoshida M Mikoshiba K 《The Journal of cell biology》2006,173(5):755-765
We developed genetically encoded fluorescent inositol 1,4,5-trisphosphate (IP3) sensors that do not severely interfere with intracellular Ca2+ dynamics and used them to monitor the spatiotemporal dynamics of both cytosolic IP3 and Ca2+ in single HeLa cells after stimulation of exogenously expressed metabotropic glutamate receptor 5a or endogenous histamine receptors. IP3 started to increase at a relatively constant rate before the pacemaker Ca2+ rise, and the subsequent abrupt Ca2+ rise was not accompanied by any acceleration in the rate of increase in IP3. Cytosolic [IP3] did not return to its basal level during the intervals between Ca2+ spikes, and IP3 gradually accumulated in the cytosol with a little or no fluctuations during cytosolic Ca2+ oscillations. These results indicate that the Ca2+ -induced regenerative IP3 production is not a driving force of the upstroke of Ca2+ spikes and that the apparent IP3 sensitivity for Ca2+ spike generation progressively decreases during Ca2+ oscillations. 相似文献
7.
Bcl-2 functionally interacts with inositol 1,4,5-trisphosphate receptors to regulate calcium release from the ER in response to inositol 1,4,5-trisphosphate 总被引:15,自引:0,他引:15
Chen R Valencia I Zhong F McColl KS Roderick HL Bootman MD Berridge MJ Conway SJ Holmes AB Mignery GA Velez P Distelhorst CW 《The Journal of cell biology》2004,166(2):193-203
Inositol 1,4,5-trisphosphate (InsP3) receptors (InsP3Rs) are channels responsible for calcium release from the endoplasmic reticulum (ER). We show that the anti-apoptotic protein Bcl-2 (either wild type or selectively localized to the ER) significantly inhibited InsP3-mediated calcium release and elevation of cytosolic calcium in WEHI7.2 T cells. This inhibition was due to an effect of Bcl-2 at the level of InsP3Rs because responses to both anti-CD3 antibody and a cell-permeant InsP3 ester were decreased. Bcl-2 inhibited the extent of calcium release from the ER of permeabilized WEHI7.2 cells, even at saturating concentrations of InsP3, without decreasing luminal calcium concentration. Furthermore, Bcl-2 reduced the open probability of purified InsP3Rs reconstituted into lipid bilayers. Bcl-2 and InsP3Rs were detected together in macromolecular complexes by coimmunoprecipitation and blue native gel electrophoresis. We suggest that this functional interaction of Bcl-2 with InsP3Rs inhibits InsP3R activation and thereby regulates InsP3-induced calcium release from the ER. 相似文献
8.
The subsecond mobilization of intracellular Ca2+ by IP3 was measured with rapid mixing techniques to determine how cells achieve rapid rises in cytosolic [Ca2+] during receptor-triggered calcium spiking. In permeabilized rat basophilic leukemia cells at 11 degrees C, more than 80% of the 0.7 fmol of Ca2+/cell sequestered by the ATP-driven pump could be released by IP3. Half of the stored Ca2+ was released within 200 ms after addition of saturating (1 microM) IP3. The flux rate was half-maximal at 120 nM IP3. Ca2+ release from fully loaded stores was highly cooperative; the Hill coefficient over the 2-40 nM range was greater than 3. The delay time of channel opening was inversely proportional to [IP3], increasing from 150 ms at 100 nM IP3 to 1 s at 15 nM, indicating that the rate-limiting step in channel opening is IP3 binding. Multiple binding steps are required to account for the observed delay and nonexponential character of channel opening. A simple model is proposed in which the binding of four IP3 molecules to identical and independent sites leads to channel opening. The model agrees well with the data for KD = 18 nM, kon = 1.2 X 10(8) M-1 s-1, and koff = 2.2 s-1. The approximately 1-s exchange time of bound IP3 indicates that the channel gating sites are distinct from binding sites having approximately 100-s exchange times that were previously found with radiolabeled IP3. The approximately 1-1s response time of [Ca2+] to a rapid increase in IP3 level can account for observed rise times of calcium spikes. 相似文献
9.
In various cell types cytosolic calcium (Ca(2+)) is an important regulator. The possible role of Ca(2+) release from the inositol 1,4,5-trisphosphate (IP(3)) receptor channel in the regulation of the phosphorylation-dephosphorylation cycle process involved in glycogen degradation by glycogen phosphorylase have theoretically investigated by using the Li-Rinzel model for cytosolic Ca(2+) oscillations. For the case of deterministic cytosolic Ca(2+) oscillations, there exists an optimal frequency of cytosolic Ca(2+) oscillations at which the average fraction of active glycogen phosphorylase reaches a maximum value, and a mutation for the average fraction of active glycogen phosphorylase occurs at the higher bifurcation point of Ca(2+) oscillations. For the case of stochastic cytosolic Ca(2+) oscillations, the fraction of active phosphorylase is strongly affected by the number of IP(3) receptor channels and the level of IP(3) concentration. Small number of IP(3) receptor channels can potentiate the sensitivity of the activity of glycogen phosphorylase. The average frequency and amplitude of active phosphorylase stochastic oscillations are increased with the level of increasing IP(3) stimuli. The various distributions for the amplitude of active glycogen phosphorylase oscillations in parameters plane are discussed. 相似文献
10.
The effect of inositol 1,4,5-trisphosphate and GTP on calcium release from rat liver microsomes 总被引:1,自引:0,他引:1
Inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) and GTP mobilized 8% and 90% of the ionophore-releaseable Ca2+ pool from rat liver microsomes, respectively. In contrast to GTP, which acted after a lag-time, the Ins(1,4,5)P3-induced Ca2+ release was immediate. Poly(ethylene glycol) inhibited the effect of Ins(1,4,5)P3 and enhanced that of GTP. Ins(1,4,5)P3 accelerated and enhanced the GTP-induced Ca2+ release. Guanylyl imidodiphosphate inhibited competitively the GTP stimulated Ca2+ release, but not the GTP-dependent phosphorylation of the Mr 17,000 and 38,000 protein bands. 相似文献
11.
The binding of many ligands to cellular receptors induces a signaling cascade which generates inositol 1,4,5-trisphosphate (IP3). IP3 binding to its receptors in various internal compartments causes a rapid Ca2+ efflux into the cytosol. We now demonstrate that chloroquine blocks ligand-induced Ca2+ mobilization without affecting IP3 synthesis. The effect is independent of the ligand employed and occurred with five unrelated ligands; namely, α2-macroglobulin-methylamine, angiotensin II, bradykinin, carbachol, and epidermal growth factor. Chloroquine, quinidine, and quinine, however, block binding of [3H]IP3 to its receptors by 90%, 88%, and 71%, respectively. These observations suggest a previously undetected mechanism by which these agents may in part function as antimalarials. J. Cell. Biochem. 64:225–232. © 1997 Wiley-Liss, Inc. 相似文献
12.
Stereospecific mobilization of intracellular Ca2+ by inositol 1,4,5-triphosphate. Comparison with inositol 1,4,5-trisphosphorothioate and inositol 1,3,4-trisphosphate. 总被引:12,自引:5,他引:7
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The isolated activation segment of pig procarboxypeptidase A binds two Tb3+ ions in a strong and specific way. In contrast, the binding of Ca2+, Cd2+ and Mg2+ is weak. The binding of Tb3+ increases the resistance of the isolated activation segment against proteolysis and competes for the binding of the carbocyanine dye Stains-All. This dye forms complexes with the activation segment showing spectral properties similar to those observed with EF-hand structures. The presented results support a previous hypothesis on the existence of two regions in the activation segment of pancreatic procarboxypeptidases structurally related to Ca2+-binding domains of the EF-hand protein family. 相似文献
13.
Influence of inositol 1,4,5-trisphosphate and guanine nucleotides on intracellular calcium release within the N1E-115 neuronal cell line 总被引:19,自引:0,他引:19
The Ca2+ accumulating properties of a nonmitochondrial intracellular organelle within cultured N1E-115 neuroblastoma cells containing an (ATP + Mg2+)-dependent Ca2+ pump were recently described in detail (Gill, D. L., and Chueh, S. H. (1985) J. Biol. Chem. 260, 9289-9297). Using both saponin-permeabilized N1E-115 cells and microsomal membranes from cells, this report describes the effectiveness of both inositol 1,4,5-trisphosphate (IP3) and guanine nucleotides in mediating Ca2+ release from this internal organelle, believed to be endoplasmic reticulum. Using permeabilized N1E-115 cells, 2 microM IP3 effects rapid release (t1/2 less than 20 s) of approximately 40% of accumulated Ca2+ releasable with 5 microM A23187. Half-maximal Ca2+ release occurs with 0.5 microM IP3, and maximal release with 3 microM IP3. Using a frozen microsomal membrane fraction isolated from lysed cells, 2 microM IP3 rapidly releases (t1/2 less than 30 s) 10-20% of A23187-releasable Ca2+ accumulated within nonmitochondrial Ca2+-pumping vesicles, although only in the presence of 3% polyethylene glycol (PEG). 10 microM GTP, but not guanosine 5'-(beta, gamma-imido)triphosphate (GMPPNP), increases the extent of release in the presence of IP3. Importantly, however, GTP alone induces a substantial release of Ca2+ (up to 40% of releasable Ca2+) with a t1/2 value (60-90 s) slightly longer than that for IP3. The effects of IP3 and GTP are approximately additive, and both effects require 3% PEG. Half-maximal Ca2+ release occurs with 1 microM GTP, with maximal release at 3-5 microM GTP; 20 microM GMPPNP has no effect on release and only slightly inhibits 5 microM GTP; 20 microM GDP promotes full release, but only after a 90-s lag, and initially inhibits the action of 5 microM GTP. Using permeabilized N1E-115 cells, 5 microM GTP with 3% PEG releases greater than 50% of releasable Ca2+; without PEG, GTP still mediates approximately 30% release of Ca2+ from cells. Neither IP3, GTP, or both together (with or without PEG) effects release of Ca2+ accumulated within synaptic plasma membrane vesicles. The profound effectiveness of GTP on Ca2+ release has important implications for intracellular Ca2+ regulation and is probably related to Ca2+ release mediated by IP3. 相似文献
14.
Sarkisov DV Gelber SE Walker JW Wang SS 《The Journal of biological chemistry》2007,282(35):25517-25526
Biological messengers can be "caged" by adding a single photosensitive group that can be photolyzed by a light flash to achieve spatially and temporally precise biochemical control. Here we report that photolysis of a double-caged form of the second messenger inositol 1,4,5-trisphosphate (IP3) triggers focal calcium release in Purkinje cell somata, dendrites, and spines as measured by two-photon microscopy. In calbindin knock-out Purkinje cells, peak calcium increased with flash energy with higher cooperativity for double-caged IP3 than for conventional single-caged IP3, consistent with a chemical two-photon effect. Spine photolysis of double-caged IP3 led to local calcium release. Uncaging of glycerophosphoryl-myo-inositol 4,5-bisphosphate (gPIP2), a poorly metabolizable IP3 analog, led to less well localized release. Thus, IP3 breakdown is necessary for spine-specificity. IP3- and gPIP2-evoked signals declined from peak with similar, slow time courses, indicating that release lasts hundreds of milliseconds and is terminated not by IP3 degradation but by intrinsic receptor dynamics. Based on measurements of spine-dendrite coupling, IP3-evoked calcium signals are expected to be at least 2.4-fold larger in their spine of origin than in nearby spines, allowing IP3 to act as a synapse-specific second messenger. Unexpectedly, single-caged IP3 led to less release in somata and was ineffective in dendrites and spines. Calcium release using caged gPIP2 was inhibited by the addition of single-caged IP3, suggesting that single-caged IP3 is an antagonist of calcium release. Caging at multiple sites may be an effective general approach to reducing residual receptor interaction. 相似文献
15.
Ching-Wen Yang Joseph L. Borowitz Palur G. Gunasekar Gary E. Isom 《Journal of biochemical and molecular toxicology》1996,11(5):251-256
Cyanide-induced neurotoxicity is associated with altered cellular Ca2+ homeostasis resulting in sustained elevation of cytosolic Ca2+. In order to characterize the effect of cyanide on intracellular signaling mechanisms, the interaction of KCN with the inositol 1,4,5-triphosphate Ca2+ signaling system was determined in the PC12 cell line. KCN in the concentration range of 1.0–100 μM produced a rapid rise in intracellular IP3 levels (peak level occurred within 60 sec); 10 μM KCN elevated intracellular levels of IP3 to 148% of control levels. This response was mediated by phospholipase C (PLC) since U73122, a specific PLC inhibitor, blocked the response. Removal of Ca2+ from the incubation medium and chelation of intracellular Ca2+ with BAPTA partially attenuate the cyanide-stimulated IP3 generation, showing that the response is partially Ca2+ dependent. Also, treatment of cells with nifedipine or LaCl3, Ca2+ channel blockers, partially blocked the generation of IP3. This study shows that cyanide in concentrations as low as 1 μM stimulates IP3 generation that may be mediated by receptor and nonreceptor IP3 production since they have differential dependence on Ca2+. It is proposed that this response is an early intracellular signaling action that can contribute to altered Ca2+ homeostasis characteristic of cyanide neurotoxicity. © 1997 John Wiley & Sons, Inc. 相似文献
16.
Bombesin stimulation of inositol 1,4,5-trisphosphate generation and intracellular calcium release is amplified in a cell line overexpressing the N-ras proto-oncogene. 总被引:4,自引:0,他引:4
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A C Lloyd S A Davies I Crossley M Whitaker M D Houslay A Hall C J Marshall M J Wakelam 《The Biochemical journal》1989,260(3):813-819
Human neutrophils and HL-60 leukaemic cells possess an NADPH oxidase which catalyses superoxide (O2-) formation and is activated by the chemotactic peptide, N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMet-Leu-Phe). In dibutyryl cyclic AMP-differentiated HL-60 cells, ATP and UTP in the presence of cytochalasin B activated O2- formation with EC50 values of 5 microM and efficacies amounting to 30% of that of fMet-Leu-Phe. The potency order of purine nucleotides in activating O2- generation was ATP = adenosine 5'-O-(3-thiotriphosphate) greater than ITP greater than dATP = ADP. Pyrimidine nucleotides activated NADPH oxidase in the potency order UTP greater than dUTP greater than CTP = TTP = UDP. Pertussis toxin completely prevented activation of NADPH oxidase by fMet-Leu-Phe and UTP, whereas the effect of ATP was only partially inhibited. ATP and UTP enhanced O2- generation induced by fMet-Leu-Phe by up to 8-fold, and primed the cells to respond to non-stimulatory concentrations of fMet-Leu-Phe. Activation of NADPH oxidase by UTP but not by ATP was inhibited by various activators of adenylate cyclase. In dimethyl sulphoxide-differentiated HL-60 cells and in human neutrophils, ATP and UTP per se did not activate NADPH oxidase, but they potentiated the effect of fMet-Leu-Phe. Our results suggest that purine and pyrimidine nucleotides act via purino- and novel pyrimidinoceptors respectively, which are coupled to guanine nucleotide-binding proteins leading to the activation of NADPH oxidase. As ATP and UTP are released from cells under physiological and pathological conditions, these nucleotides may play roles as intercellular signal molecules in the activation of O2- formation. 相似文献
17.
Considerable insight into intracellular Ca2+ responses has been obtained through the development of whole cell models that are based on molecular mechanisms, e.g., single channel kinetics of the inositol 1,4,5-trisphosphate (IP3) receptor Ca2+ channel. However, a limitation of most whole cell models to date is the assumption that IP3 receptor Ca2+ channels (IP3Rs) are globally coupled by a “continuously stirred” bulk cytosolic [Ca2+], when in fact open IP3Rs experience elevated “domain” Ca2+ concentrations. Here we present a 2N+2-compartment whole cell model of local and global Ca2+ responses mediated by N=100,000 diffusely distributed IP3Rs, each represented by a four-state Markov chain. Two of these compartments correspond to bulk cytosolic and luminal Ca2+ concentrations, and the remaining 2N compartments represent time-dependent cytosolic and luminal Ca2+ domains associated with each IP3R. Using this Monte Carlo model as a starting point, we present an alternative formulation that solves a system of advection-reaction equations for the probability density of cytosolic and luminal domain [Ca2+] jointly distributed with IP3R state. When these equations are coupled to ordinary differential equations for the bulk cytosolic and luminal [Ca2+], a realistic but minimal model of whole cell Ca2+ dynamics is produced that accounts for the influence of local Ca2+ signaling on channel gating and global Ca2+ responses. The probability density approach is benchmarked and validated by comparison to Monte Carlo simulations, and the two methods are shown to agree when the number of Ca2+ channels is large (i.e., physiologically realistic). Using the probability density approach, we show that the time scale of Ca2+ domain formation and collapse (both cytosolic and luminal) may influence global Ca2+ oscillations, and we derive two reduced models of global Ca2+ dynamics that account for the influence of local Ca2+ signaling on global Ca2+ dynamics when there is a separation of time scales between the stochastic gating of IP3Rs and the dynamics of domain Ca2+. 相似文献
18.
Characterization of inositol 1,4,5-trisphosphate-stimulated calcium release from rat cerebellar microsomal fractions. Comparison with [3H]inositol 1,4,5-trisphosphate binding. 总被引:4,自引:1,他引:3
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The abilities of D-myo-inositol phosphates (InsPs) to promote Ca2+ release and to compete for D-myo-[3H]-inositol 1,4,5-trisphosphate [( 3H]Ins(1,4,5)P3) binding were examined with microsomal preparations from rat cerebellum. Of the seven InsPs examined, only Ins(1,4,5)P3, Ins(2,4,5)P3 and Ins(4,5)P2 stimulated the release of Ca2+. Ca2+ release was maximal in 4-6 s and was followed by a rapid re-accumulation of Ca2+ into the Ins(1,4,5)P3-sensitive compartment after Ins(1,4,5)P3, but not after Ins(2,4,5)P3 or Ins(4,5)P2. Ca2+ re-accumulation after Ins(1,4,5)P3 was also faster than after pulse additions of Ca2+, and coincided with the metabolism of [3H]Ins(1,4,5)P3. These data suggest that Ins(1,4,5)P3-induced Ca2+ release and the accompanying decrease in intraluminal Ca2+ stimulate the Ca2+ pump associated with the Ins(1,4,5)P3-sensitive compartment. That this effect was observed only after Ins(1,4,5)P3 may reflect differences in either the metabolic rates of the various InsPs or an effect of the Ins(1,4,5)P3 metabolite Ins(1,3,4,5)P4 to stimulate refilling of the Ins(1,4,5)P3-sensitive store. InsP-induced Ca2+ release was concentration-dependent, with EC50 values (concn. giving half-maximal release) of 60, 800 and 6500 nM for Ins(1,4,5)P3, Ins(2,4,5)P3 and Ins(4,5)P2 respectively. Ins(1,4,5)P3, Ins(2,4,5)P3 and Ins(4,5)P2 also competed for [3H]Ins(1,4,5)P3 binding, with respective IC50 values (concn. giving 50% inhibition) of 100, 850 and 13,000 nM. Comparison of the EC50 and IC50 values yielded a significant correlation (r = 0.991). These data provide evidence of an association between the [3H]Ins(1,4,5)P3-binding site and the receptor mediating Ins(1,4,5)P3-induced Ca2+ release. 相似文献
19.
Inositol 1,4,5-trisphosphate and 5'-GTP induce calcium release from different intracellular pools 总被引:6,自引:0,他引:6
It has been shown recently by several groups that 5'-GTP can release calcium from intracellular compartments independently from inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) by a mechanism which seems to be different from that used by Ins(1,4,5)P3. We report here for the first time that the 5'-GTP-sensitive and the Ins(1,4,5)P3-sensitive calcium pools reside in different intracellular compartments. 相似文献