Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

It has become clear that calcium is an important mediator in the transduction of signals due to ligand binding to cell surface receptors. Cytosolic calcium is typically maintained at low levels in both muscle and non-muscle cells and intracellular sequestering of calcium appears to be important in this process. The identification of intracellular calcium pools has been the subject of much recent study, and it has been proposed that such pools would contain three components: a calcium-activated pump or Ca(2+)-ATPase, a calcium channel such as the inositol trisphosphate receptor or ryanodine receptor, and a high-capacity calcium-binding protein such as calsequestrin or calreticulin. We report here on the localization of two components, the organellar Ca(2+)-ATPase (SERCA) and calreticulin, in neuronal tissues. Using immunofluorescence and subcellular fractionation, we have found that for the most part, these two proteins do not co-localize in neuron cell bodies, dendrites, or axons; but may co-localize at the axon terminal.
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PMID:Differences in the subcellular localization of calreticulin and organellar Ca(2+)-ATPase in neurons. 838 14

Ouabain increases atrial natriuretic peptide (ANP) secretion. When isolated superfused rat left atria were paced at 2 Hz, ouabain at concentrations of 50, 100, and 200 microM increased ANP secretion by 2.0 +/- 0.3-, 3.2 +/- 0.5-, and 4.2 +/- 0.5-fold, respectively. In this study, we examine the mechanism of ouabain-stimulated ANP secretion using the dose of 100 microM. To determine whether calcium played a role, atria were superfused with the calcium antagonist lanthanum. Superfusion with 2 mM LaCl3 completely inhibited ouabain-stimulated secretion, suggesting that calcium influx and/or sarcoplasmic reticulum (SR) calcium release provide essential sources of calcium for the stimulatory pathway. To determine the contribution of calcium from the SR, atria were superfused with ryanodine, an agent that depletes the SR of calcium. Superfusion with 1 microM ryanodine inhibited ouabain-stimulated secretion by 47%. Inhibition of Na+,K(+)-ATPase allows sodium to accumulate in the cell. A rise in intracellular sodium alters Na(+)-Ca2+ exchange, leading to an increase in cytosolic calcium. To determine the mechanism of sodium entry, atria were superfused with 5-(N,N-hexamethylene)amiloride (HMA), an inhibitor of Na(+)-H+ exchange, or with bumetanide, an inhibitor of Na(+)-K(+)-Cl- cotransport. Superfusion with 25 microM HMA inhibited ouabain-stimulated secretion by 71%; however, 100 microM bumetanide had no significant effect on secretion. Ouabain failed to stimulate ANP secretion by nonpaced (nonbeating) atria. Likewise, superfusion with the combination of ryanodine (1 microM) and the calcium channel antagonist israpidine (10 microM) totally blocked ouabain-stimulated ANP secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ouabain. A stimulator of atrial natriuretic peptide secretion and its mechanism of action. 838 95

Resistance of tumors to a variety of chemotherapeutic agents presents a major problem in cancer treatment. The gene responsible for multidrug resistance, termed mdr1, encodes a membrane glycoprotein (P-glycoprotein) that acts as a pump to transport various cytotoxic agents. The P-glycoprotein has been shown to bind anticancer drugs and several resistance-reversing agents including calcium channel blockers, and to be an ATPase. The P-glycoprotein was found to function in blood-brain barrier. The implication of the P-glycoprotein in relation to therapy is discussed.
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PMID:[Structure and function of P-glycoprotein in antitumor agent resistance; implication for clinical setting]. 853 80

Magnesium (Mg), a cofactor in numerous enzymatic reactions, is often ignored by clinicians, as the symptomatology of Mg depletion is not specific and usually associated with that of the cause of the depletion. Furthermore, the plasma Mg concentration (0.8 to 1.1 mmol.L-1) is only equivalent to one percent of the total body content. A Mg deficit may exist while plasma Mg concentration is normal. Therefore other techniques for Mg assessment, such as the repletion test, as well as red blood cell and lymphocyte concentrations have been used. A renewed interest for Mg occurred as numerous studies have shown the therapeutic efficiency of Mg and as the mechanisms of its haemodynamic effects have been recognized. Mg regulates Na-K-ATPase activity, K channels activity and, most of all, it is a natural calcium channel blocking agent. These properties explain its important place in electrophysiology of myocardial cells and the effects on the tension of smooth muscles, resulting in a vasodilation and a bronchodilation respectively. The antagonistic effect of Mg on calcium decreases the presynaptic release of acetylcholine at the neuromuscular junction and the release of epinephrine at the peripheral sympathetic nerves and the adrenals. Mg potentiates the effect of non-depolarizing muscle relaxants. A Mg deficiency occurs often in ICU patients, in alcoholics and during use of diuretics. Simultaneous administration of Mg is often required for treatment of potassium deficiency. Mg has an anti-arrhythmic effect towards digoxin-mediated dysrhythmias and torsades de pointes, and can be efficient in other arrhythmias. Systematic use of Mg seems to decrease mortality of acute myocardial infarction and is justified during cardiac surgery, often associated with hypomagnesemia, because of vasodilation of coronary arteries and in order to prevent occurrence of arrhythmias. Mg, because of its calcium channel blocking properties and as it lowers the release of epinephrine, is indicated for surgery of pheochromocytoma. In eclamptic and pre-eclamptic patients, the use of Mg is valuable, but not as an anti-epileptic agent. Other clinical uses of Mg have been proposed, but they are either anecdotal or of uncertain efficiency.
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PMID:[Indications for the use of magnesium in anesthesia and intensive care]. 857 7

Ouabain, an Na+K+ATPase inhibitor, increases the release of acetylcholine (ACh) from various preparations in a Ca2+ -independent way. However, in other preparations the release of ACh evoked by ouabain is dependent on the presence of extracellular calcium. In the present study, we have labeled the ACh of myenteric plexus longitudinal muscles of guinea pig ileum and compared the effect of calcium channel blockers on ouabain-evoked release of [3H]ACh. Release of [3H]ACh evoked by ouabain is dose dependent and decreased markedly in the absence of calcium or in the presence of cadmium, a nonspecific calcium channel blocker. N-type calcium channel blockage by the omega-conotoxins GVIA (selective N-type calcium channel blocker) and MVIC (a nonselective calcium channel blocker) inhibited by 45 and 55%, respectively, the release of [3H]ACh. L-type calcium channel suppression by low concentrations of verapamil, nifedipine, and diltiazem had no effect on the release of [3H]ACh. The release of transmitter was also not affected significantly by nickel, a T-type calcium channel blocker. In addition, omega-agatoxin-IVA, at concentrations that block P- and Q-type calcium channels, did not affect significantly the release of [3H]ACh. Thus, extracellular Ca2+ is essential for the release of ACh induced by ouabain from guinea pig ileum myenteric plexus. In this preparation, the N-type calcium channel plays a dominant role in transmitter release evoked by inhibition of Na+K+-ATPase, but other routes of calcium entry in addition to these channels can also support the release of neurotransmitter induced by ouabain.
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PMID:Inhibition of Na+,K+-ATPase by ouabain opens calcium channels coupled to acetylcholine release in guinea pig myenteric plexus. 862 96

Measurements of free calcium ion concentration in the sarcoplasmic reticulum ([Ca2+]SR) and an evaluation of its relationship to changes in cytosolic free calcium and energy state of the cell, as well as heterogeneity of the SR calcium pool, were performed using 19F NMR in Langendorff perfused rabbit hearts loaded with acetoxymethyl ester of 1,2-bis(2-amino-5,6-difluorophenoxy)ethane-N,N,N',N'-tetraacetic acid. We report a base-line time-average [Ca2+]SR value of 1.5 mM (n = 13) in the beating heart, similar to the value measured at diastole. We further report that [Ca2+]SR decreases by approximately 30% at the start of systole and that there is no evidence of spacial heterogeneity in [Ca2+]SR during the contraction cycle. However, there appears to be a heterogeneous response to SR calcium channel release activator (caffeine) and SR calcium-ATPase inhibitor (cyclopiazonic acid), consistent with studies suggesting that there are subpopulations of SR. Raising cytosolic free calcium by depolarizing the cell with 30 mM extracellular KCl, resulted in an increase in [Ca2+]SR; however, the calcium gradient was unchanged. Lowering cell phosphorylation potential, which would reduce the free energy available for the SR Ca2+-ATPase, leads to a decrease in the calcium gradient across the SR, but this reduced gradient was primarily due to an increase in cytosolic free calcium and not a net release of SR calcium.
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PMID:Measurement of free Ca2+ in sarcoplasmic reticulum in perfused rabbit heart loaded with 1,2-bis(2-amino-5,6-difluorophenoxy)ethane-N,N,N',N'-tetraacetic acid by 19F NMR. 863 64

Free radical-induced physiopathologies are generally thought to be mediated by membrane injuries. Using a pro-oxidant model induced by dietary magnesium deficiency, we have recently shown that skeletal muscle lesions occurred with a rise in the calcium level and enhanced free radical production. In this study, we investigated the physicochemical and biochemical properties of sarcoplasmic reticulum membranes isolated from hind limb muscles of weanling male rats pair fed magnesium-deficient or control diets for 12 d. The calcium-induced calcium efflux from preloaded vesicles was increased in membranes isolated from Mg-deficient rat muscle. In agreement with this latter observation, we demonstrated increased ryanodine binding affinity of the calcium channel. The Ca2(+)-ATPase activity of the pump was shown to be reduced. The viscosity state of the membranes, assessed by 1,6-diphenyl-1,3,5-hexatriene fluorescence anisotropy, was significantly increased in Mg-deficient membranes. Moreover, these membranes demonstrated an increased content of protein carbonyls as compared with controls. These functional as well as structural changes are closed to those described in sarcoplasmic reticulum membranes oxidatively modified in vitro. Together, these data fitted well with the concept that free radical-induced membrane damages resulting in calcium overload may be at the origin of skeletal muscle lesion during Mg-deficiency.
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PMID:Functional alterations in sarcoplasmic reticulum membranes of magnesium-deficient rat skeletal muscle as consequences of free radical-mediated process. 872 13

We have investigated the production of diazepam-binding inhibitor (DBI)-related peptides by astrocytes in primary culture and we have determined the effect of the octadecaneuropeptide DBI[33-50] (ODN) on the intracellular calcium concentration ([Ca2+]i) in astrocytes. Immunocytochemical labeling with antibodies against ODN showed that cultured astrocytes retain their ability to synthesize DBI in vitro. Cultured astrocytes were also found to release substantial amounts of ODN-immunoreactive material, and a brief exposure of astrocytes to a depolarizing potassium concentration resulted in a 5-fold increase in the rate of release of the ODN-like peptide. Microfluorimetric measurement of [Ca2+]i with the fluorescent probe indo-1 showed that nanomolar concentrations of ODN induced a marked increase in [Ca2+]i. The stimulatory effect of ODN on [Ca2+]i was not affected by calcium channel blockers or by incubation in Ca(2+)-free medium. In contrast, thapsigargin, an inhibitor of microsomal Ca(2+)-ATPase activity, totally abolished the ODN-induced increase in [Ca2+]i. Repeated pulses of ODN caused attenuation of the response, indicating the existence of a desensitization phenomenon. Preincubation of astrocytes with pertussis toxin totally blocked the effect of ODN on [Ca2+]i. The present study indicates that ODN-related peptides are synthesized and released by glial cells. Our results also show that synthetic ODN induces calcium mobilization from an intracellular store through stimulation of pertussis toxin-sensitive G protein. Taken together, these data suggest that endozepines act as paracrine and/or autocrine factors controlling the activity of astroglial cells.
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PMID:The endogenous benzodiazepine receptor ligand ODN increases cytosolic calcium in cultured rat astrocytes. 873 63

1. Unilateral left renal artery occlusion for 1 h in a group of 8 untreated female Sprague-Dawley rats resulted in oliguric acute renal failure (ARF) persisting for more than 6 h after reflow, i.e. after reperfusion of the kidney by removal of the arterial clamp. In a second group of 8 rats with left unilateral ARF the effects of levemopamil (L), a calcium entry blocker with 5-hydroxytryptamine2 (5-HT2) receptor antagonistic properties, were studied. Rats received L as a continuous infusion (6 mg kg-1 h-1) from 1 h before ischaemia until 6 h after reflow. 2. Endogenous creatinine clearance, an estimate of glomerular filtration rate (GFR), of left ischaemic kidneys of untreated rats was almost completely abolished and urine flow was 0.05 +/- 0.02 and 0.03 +/- 0.01 ml h-1 100 g-1 body weight (body wt.) at 2 and at 6 h of reflow, respectively. In contrast, left ischaemic kidneys of L-treated rats revealed significantly higher GFR (0.10 +/- 0.02 and 0.03 +/- 0.01 ml min-1 g-1 kidney weight (k.wt.); P < 0.01) and urine flow (0.51 +/- 0.05 and 0.15 +/- 0.04 ml h-1 100 g-1 body wt.; P < 0.05) at 2 and 6 h of reflow, respectively. 3. At 6 h of reflow, mitochondria from the cortex of left ischaemic kidneys of untreated rats showed significantly reduced ATP synthesis when compared to right intact kidneys (0.06 +/- 0.02 vs 0.26 +/- 0.02 mumol ATP mg-1 protein min-1 (P < 0.01)). In contrast, in L-treated rats, ATP synthesis of left ischaemic kidneys was largely preserved (0.17 +/- 0.01 mumol ATP mg-1 protein min-1). 4. Ischaemia of left kidneys resulted in a significant decrease in medullary Na-K-ATPase activity to 9.6 +/- 2.4 as compared to 20.4 +/- 3.7 mumol P(i) h-1 mg-1 protein in the intact right kidneys which was not prevented by L (9.4 +/- 2.4 mumol P(i) h-1 mg-1 protein). 5. In untreated rats the calcium content in cortical mitochondria from left ischaemic kidneys had risen 2 fold to 23.0 +/- 1.8 at 6 h of reflow as compared to 12.2 +/- 0.3 nmol mg-1 protein in right intact kidneys (P < 0.01). This rise in mitochondrial calcium was not significantly attenuated by treatment with L (19.9 +/- 1.7 nmol mg-1 protein). 6. The results show that L transiently converted oliguria into non-oliguria during the early phase after reflow in ischaemic ARF, i.e. after reperfusion following 1 h of complete interruption of renal perfusion. The present data suggest indirectly that the 5-HT2-antagonistic properties of L rather than its calcium channel blocking action maintains GFR at low level and protects mitochondrial function early after reflow in this model of ischaemic ARF.
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PMID:Calcium entry and 5-HT2 receptor blockade in oliguric ischaemic acute renal failure: effects of levemopamil in conscious rats. 888 35

Intracellular calcium ions are, in addition to free radicals, an important mediator of tissue destruction following traumatic injury to the spinal cord. In vivo measurements of calcium in the interstitial space and in the tissue suggest the occurrence of a posttraumatic shift of calcium from the extracellular to the intracellular compartment at the injury site. No information is, however, available on the posttraumatic changes of calcium in the intracellular compartment, where the ion exerts its crucial messenger function. We developed an in vitro model of local traumatic spinal injury, using a spinal cord slice preparation, allowing us to investigate injury-related changes of intracellular free calcium. The injury consisted of the impact of a small needle, and intracellular free calcium was measured with fura-2. Application of the injury at different places within the gray matter caused a transient and reproducible increase in the fura-2 fluorescence ratio. This injury-induced ratio increase was largely, but not completely, suppressed under zero extracellular calcium conditions. It was also largely depressed in the presence of high extracellular potassium and in the absence of extracellular sodium. It was modestly depressed by the calcium channel blocker nifedipin, by the calcium release channel blocker dantrolene, and by the gap junction blockers halothane and octanol. The calcium channel blocker flunarizine, the N-methyl D-aspartate (NMDA)-receptor-channel blocker MK-801 and the endoplasmic reticulum calcium-ATPase blocker thapsigargin had no effect. The experiments suggest that injury is associated with an increase in intracellular free calcium that is mediated by calcium influx, in part via L-type calcium channels. They furthermore give evidence that sodium influx and gap junctions are involved in these injury-associated changes of intracellular free calcium.
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PMID:Changes of intracellular free calcium following mechanical injury in a spinal cord slice preparation. 900 41


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