Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Regulation of many cell systems has been shown to be mediated by Inositol 1,4,5-trisphosphate which causes a release of calcium from intracellular sites. We have shown that release of Ca2+ from sarcoplasmic reticulum microsomes was not stimulated by IP3. The phorbol ester, TPA, also had no effect on Ca2+ release or Ca2+ ATPase activity. Thus, it is unlikely that the breakdown of polyphosphatidylinositides serves as a second messenger to mediate release of Ca2+ in skeletal muscle.
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PMID:Inositol 1,4,5-trisphosphate is not effective in releasing calcium from skeletal sarcoplasmic reticulum microsomes. 315 84

Ca2+-specific minielectrodes were used to monitor changes in the ambient free Ca2+ concentration [( Ca2+]a) maintained by the intracellular organelles of permeabilized GH3 cells. Mitochondria maintained a [Ca2+]a steady state of around 500 nM and displayed a very high capacity for Ca2+ uptake. A nonmitochondrial pool, tentatively identified as the endoplasmic reticulum (ER), displayed higher affinity for Ca2+ by maintaining a steady state of approximately 170 nM. The capacity of this pool was around 10 nmol/mg cell protein. Inositol 1,4,5-trisphosphate (InsP3) released Ca2+ specifically from the ER, with an EC50 of approximately 2 microM, and gave maximal release of around 4 nmol Ca2+/mg of cell protein. Repeated InsR3 additions under conditions allowing for functional mitochondrial transport resulted in successively attenuated peaks, leading eventually to the depletion of the InsP3 sensitive portion of the ER. However, Ca2+ could still be released from the total ER pool with the ATPase inhibitor, vanadate. This InsP3-insensitive store did not reaccumulate InsP3 releasable Ca2+ nor could it directly refill the sensitive pool. However, the attenuation of the InsP3 responses could be overcome by repleting the sensitive pool with exogenous Ca2+ or by inhibiting Ca2+ uptake into the mitochondria. The results suggest: 1) the ER is the major intracellular organelle buffering Ca2+ in nonstimulated GH3 cells; 2) InsP3 releases Ca2+ from only a portion of the ER; 3) the InsP3-sensitive and -insensitive ER pools are functionally distinct; 4) InsP3 addition results in a transfer of Ca2+ from the ER to the mitochondria.
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PMID:Inositol 1,4,5-trisphosphate and intracellular Ca2+ homeostasis in clonal pituitary cells (GH3). Translocation of Ca2+ into mitochondria from a functionally discrete portion of the nonmitochondrial store. 348 68

Inositol 1,4,5-trisphosphate (IP3) was found to release Ca2+ from presynaptic nerve endings (synaptosomes) made permeable with saponin. ATP-dependent Ca2+ uptake was carried out until equilibrium was reached. Addition of IP3 produced a rapid release of Ca2+, which was complete within 60 sec, followed by Ca2+ reaccumulation to the original level in 5-7 min. Cholinergic receptor stimulation with muscarine also produced a similar Ca2+ release from synaptic endoplasmic reticulum. Ca2+ release by IP3 was not detectable in the absence of the mitochondrial inhibitors oligomycin or sodium azide. Reaccumulation of Ca2+ was prevented by the presence of vanadate, a potent inhibitor of Ca2+/Mg2+ ATPase. Half maximal and near complete release of Ca2+ took place at 0.4 microM and 3 microM IP3 concentrations, respectively. These studies demonstrate for the first time IP3 mobilization of Ca2+ from endoplasmic reticulum within synaptic plasma membranes.
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PMID:Inositol 1,4,5-trisphosphate induced mobilization of Ca2+ from rat brain synaptosomes. 349 57

In neutrophils, Ca2+ influx across the plasma membrane occurs in response to a variety of agonists. It plays an important role in the regulation of neutrophil function, in particular exocytosis and release of inflammatory mediators. Using the combination of patch clamp and microfluorimetry techniques, we have found the following characteristics of neutrophil Ca2+ influx: (a) neutrophils do not possess voltage-dependent Ca2+ channels; (b) Ca2+ influx is activated by depletion of intracellular Ca2+ stores, either by Ins(1,4,5)P3, or by Ca(2+)-ATPase inhibitors; (c) Ca2+ influx is not activated by [Ca2+]i elevations and not associated with the activation of non-selective cation channels; (d) Ca2+ influx is associated with the activation of a small, voltage-independent current through a highly Ca(2+)-selective conductance. The current was only seen upon depletion of intracellular Ca2+ stores and showed a pharmacological profile similar to the fluorimetrically detected Ca2+ influx.
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PMID:[Characterization of Ca2+ influx in human neutrophils using the patch clamp technique]. 759 6

D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] inhibits human red blood cell (RBC) Ca(2+)-stimulable, Mg(2+)-dependent adenosine triphosphatase (Ca(2+)-ATPase) activity in vitro. Because we have previously shown that adrenergic receptors exist on the human mature RBC membrane and can modulate Ca(2+)-ATPase activity, we examined the possibility that a guanine nucleotide regulatory protein (G protein) mediated the Ins(1,4,5)P3 effect. Guanosine 5'-O-(3-thiotrisphosphate) (GTP gamma S) 10(-4) mol/L also inhibited RBC Ca(2+)-ATPase activity. Pertussis toxin 200 ng/mL blocked the effects of both Ins(1,4,5)P3 and GTP gamma S on Ca(2+)-ATPase activity. In separate studies, pertussis toxin-catalyzed adenosine diphosphate (ADP) ribosylation was shown to occur in RBC membranes under conditions in which measurements of Ca(2+)-ATPase activity were performed. When Ins(1,4,5)P3 10(-7) mol/L and GTP gamma S 10(-6) mol/L were added to membranes concurrently, their inhibitory actions on the enzyme were additive. At greater concentrations of Ins(1,4,5)P3 (10(-6) to 10(-5) mol/L) and GTP gamma S (10(-4) mol/L), the inositol phosphate reversed the inhibitory effect of GTP gamma S. These observations indicate that the novel effect of Ins(1,4,5)P3 on the activity of a plasma membrane Ca(2+)-ATPase depends at least in part on the action of a pertussis toxin-susceptible G protein.
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PMID:Inositol phosphates modulate human red blood cell Ca(2+)-adenosine triphosphatase activity in vitro by a guanine nucleotide regulatory protein. 761 44

Rabbit pancreatic acinar cells, permeabilized by saponin treatment, rapidly accumulated 3.5 nmol of Ca2+/mg protein in an energy-dependent pool when incubated at an ambient free Ca2+ concentration of 100 nM. Maximal loading of the internal stores was reached at 10 min and remained unchanged thereafter. Complete inhibition of the Ca2+ pump with thapsigargin revealed that this plateau was the result of a steady-state between slow Ca2+ efflux and ATP-driven Ca2+ uptake. Sixty percent of the pool could be released by Ins(1,4,5)P3, whereas GTP released another twenty percent. The striking finding of this study is that the energy-dependent store could also be released by ruthenium red. Uptake experiments in the presence of ruthenium red revealed that the dye, at concentrations below 100 microM, selectively reduced the size of the Ins(1,4,5)P3-releasable pool. Ruthenium red had no effect on the half-maximal stimulatory concentration of Ins(1,4,5)P3. At concentrations beyond 100 microM, the dye also affected the GTP-releasable pool. Comparison with thapsigargin revealed that ruthenium red released Ca2+ from stores loaded to steady-state at a rate markedly faster than can be explained by inhibition of the ATPase alone. From the data presented, we concluded that ruthenium red selectively releases Ca2+ from the Ins(1,4,5)P3-sensitive store by activating a Ca2+ release channel, whereas Ca2+ release from the GTP-sensitive store is predominantly caused by inhibition of the Ca2+ pump. The postulated ruthenium red-sensitive Ca2+ release channel might be similar to the ryanodine-receptor in muscle.
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PMID:Ruthenium red selectively depletes inositol 1,4,5-trisphosphate-sensitive calcium stores in permeabilized rabbit pancreatic acinar cells. 769 65

The human neuroblastoma cell line SH-SY5Y, maintained at confluence for 14 days, released [3H]-noradrenaline ([3H]NA) when stimulated with either the muscarinic receptor agonist methacholine or bradykinin. The major fraction of release was rapid, occurring in < 10 s, whereas nicotine-evoked release was slower. When the extracellular [Ca2+]e) was buffered to approximately 50-100 nM, release evoked by nicotine was abolished, whereas that in response to methacholine or bradykinin was reduced by approximately 50% with EC50 values of -5.46 +/- 0.05 M and -7.46 +/- 0.06 M (log 10), respectively. Methacholine and bradykinin also produced rapid elevations of both inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] and intracellular free [Ca2+] ([Ca2+]i). These elevations were reduced at low [Ca2+]e and under these conditions the EC50 values for peak elevation of [Ca2+]i were -6.00 +/- 0.14 M for methacholine and -7.95 +/- 0.34 M for bradykinin (n = 3 for all EC50 determinations). At low [Ca2+]e, depletion of nonmitochondrial intracellular Ca2+ stores with the Ca(2+)-ATPase inhibitor thapsigargin produced a transient small elevation of [Ca2+]i and a minor release of [3H]NA. At low [Ca2+]e, thapsigargin abolished elevation of [Ca2+]i in response to methacholine and bradykinin and completely inhibited their stimulation of [3H]NA release. It is proposed, therefore, that Ca2+ release from Ins (1,4,5)P3-sensitive stores is a major trigger of methacholine- and bradykinin-evoked [3H]NA release in SH-SY5Y cells.
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PMID:Mobilization of inositol 1,4,5-trisphosphate-sensitive Ca2+ stores supports bradykinin- and muscarinic-evoked release of [3H] noradrenaline from SH-SY5Y cells. 786 Nov 49

In many cell types, emptying of intracellular Ca2+ stores after application of inhibitors of the intracellular Ca(2+)-ATPase (e.g. thapsigargin) is astonishingly rapid. It was the aim of this study to elucidate the underlying mechanism. We first compared thapsigargin-induced emptying of intracellular Ca2+ stores in intact and homogenized HL-60 granulocytes. Thapsigargin-induced Ca2+ release was rapid in intact cells (33.9 +/- 4.9% of store content/min), but it was slow in permeabilized or homogenized cells (7.7 +/- 3.9 and 12 +/- 3.8% of store content/min respectively). To study whether the Ins(1,4,5)P3 receptor might be involved in thapsigargin-induced Ca2+ release, we tested the effect of heparin, a competitive Ins(1,4,5)P3 antagonist. In homogenized and permeabilized preparations, heparin did not interfere with thapsigargin-induced Ca2+ release. In contrast, when introduced into intact cells by an endocytosis/osmotic-shock procedure, heparin, but not the inactive de-N-sulphated heparin, decreased the rate of Ca2+ release by approx. 70%. Heparin inhibited Ca2+ release in response to the Ins(1,4,5)P3-generating receptor agonist N-formylmethionyl-leucyl-phenylalanine (f-MLP) (50 nM) and to thapsigargin (50 nM) at comparable concentrations. Heparin inhibition was competitive for f-MLP-induced, but not for thapsigargin-induced, Ca2+ release. In permeabilized cells, the addition of low Ins(1,4,5)P3 concentrations before thapsigargin increased the rate of thapsigargin-induced Ca2+ release 4-fold. Taken together, our results suggest that the rapid Ca(2+)-ATPase-inhibitor-induced Ca2+ release is due to a partial activation of the Ins(1,4,5)P3 receptor in resting cells. This implies Ca2+ cycling across the membrane of Ins(1,4,5)P3-sensitive Ca2+ stores in resting cells.
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PMID:Rapid heparin-sensitive Ca2+ release following Ca(2+)-ATPase inhibition in intact HL-60 granulocytes. Evidence for Ins(1,4,5)P3-dependent Ca2+ cycling across the membrane of Ca2+ stores. 806 1

The effect of the putative inhibitor of phospholipase C activity, U73122, on the Ca2+ sequestering and releasing properties of internal Ca2+ stores was studied in both permeabilized and intact rabbit pancreatic acinar cells. U73122 dose dependently inhibited ATP-dependent Ca2+ uptake in the inositol (1,4,5)-trisphosphate-[Ins(1,4,5)P3]-sensitive, but not the Ins(1,4,5)P3-insensitive, Ca2+ store in acinar cells permeabilized by saponin treatment. In a suspension of intact acinar cells, loaded with the fluorescent Ca2+ indicator, Fura-2, U73122 alone evoked a transient increase in average free cytosolic Ca2+ concentration ([Ca2+]i,av), which was largely independent of external Ca2+. Addition of U73122 to cell suspensions prestimulated with either cholecystokinin octapeptide or JMV-180 revealed an inverse relationship in size between the U73122- and the agonist-evoked [Ca2+]i,av transient. Moreover, thapsigargin-induced inhibition of intracellular Ca(2+)-ATPase activity resulted in a [Ca2+]i,av transient, the size of which was not different following maximal prestimulation with either U73122 or agonist. These observations suggest that U73122 selectively affects the Ins(1,4,5)P3- casu quo agonist-sensitive internal Ca2+ store, whereas thapsigargin affects both the Ins(1,4,5)P3-sensitive and -insensitive Ca2+ store. Digital-imaging microscopy of Fura-2-loaded acinar cells demonstrated that U73122, in contrast to thapsigargin, evoked sustained oscillatory changes in [Ca2+]i. The U73122-evoked oscillations were abolished in the absence of external Ca2+. The ability of U73122 to generate external Ca(2+)-dependent Ca2+ oscillations suggests that depletion of the agonist-sensitive store leads to an increase in Ca2+ permeability of the plasma membrane and that the Ins(1,4,5)P3-insensitive Ca2+ pool is necessary for the Ca2+ oscillations.
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PMID:Induction of Ca2+ oscillations by selective, U73122-mediated, depletion of inositol-trisphosphate-sensitive Ca2+ stores in rabbit pancreatic acinar cells. 807 41

The influence of membrane potential (Vm) on cytoplasmic calcium ([Ca2+]i) oscillations during the sustained extracellular Ca(2+)-dependent phase of the Ca2+ signaling response to gonadotropin-releasing hormone (GnRH) was analyzed in cultured pituitary gonadotrophs. In agonist- and inositol (1,4,5)-trisphosphate (Ins(1,4,5)P3)-stimulated cells, sustained [Ca2+]i oscillations were extinguished by hyperpolarization after 3-15 min despite the availability of Ca2+ in the extracellular medium. Single depolarizing pulses transiently restored the amplitude of the sustained spiking in a dihydropyridine- and extracellular Ca(2+)-sensitive manner. The responses to depolarization showed a marked dependence on Vm that was correlated with the steady-state inward Ca2+ current. In addition, repetitive application of brief depolarizing pulses modulated the frequency of agonist- and Ins(1,4,5)P3-controlled spiking; depolarization pulses at frequencies lower than the intrinsic rate of episodic Ca2+ release triggered large transients between the autonomous spikes, whereas higher frequencies of depolarizing pulses overcame the original Ca2+ spiking frequency. These extrinsically driven and extracellular Ca(2+)-dependent oscillations were sensitive to the Ca(2+)-ATPase blocker, thapsigargin, but not to ryanodine. On the other hand, spontaneous firing and application of depolarizing pulses to nonstimulated cells failed to induce thapsigargin-sensitive oscillations. These findings demonstrate that the pattern of Ca2+ signaling in gonadotrophs does not depend exclusively on the Ins(1,4,5)P3 concentration, but also on the excitable status of the cell. Such modulation of the Ins(1,4,5)P3-controlled Ca2+ signaling system by changes in Vm could provide a mechanism for the integration of multiple inputs that utilize diverse signal transduction pathways.
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PMID:Membrane potential regulates inositol 1,4,5-trisphosphate-controlled cytoplasmic Ca2+ oscillations in pituitary gonadotrophs. 810 57


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