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)

Noninvasive, self-referencing calcium (Ca2+) electrodes were used to study the mechanisms by which 5-hydroxytryptamine (5-HT) affects net Ca2+ flux across the sarcolemma of myocytes from ventricular trabeculae (from a marine gastropod, Busycon canaliculatum). Treatment of isolated trabeculae with 5-HT causes a net Ca2+ efflux, which is 30% blocked by verapamil. These findings suggest that the efflux is in part the result of a previous Ca2+ influx through L-type Ca2+ channels and is due to a rapid Ca2+ extrusion mechanism inherent to the sarcolemma of these myocytes. 5-HT-induced net Ca2+ efflux is also reduced by about 40% by treatment with a sodium (Na+)-free, lithium (Li+)-substituted saline, which shuts down the Na-Ca exchanger during Ca2+ extrusion. Cyclopiazonic acid (CPA), an inhibitor of the sarcoplasmic reticulum (SR) Ca2+ ATPase, almost completely abolishes the 5-HT-induced net Ca2+ efflux, suggesting that the SR rather than the extracellular pool is the primary Ca2+ reservoir serving 5-HT-induced excitation.
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PMID:5-Hydroxytryptamine stimulates net Ca2+ flux in the ventricular muscle of a mollusc (Busycon canaliculatum) during cardioexcitation. 1144 76

Low concentrations of halothane and isoflurane can release acetylcholine in an extracellular Ca(2+)-independent manner. In the present study, a cholinergic cell line (SN56) was used to examine whether release of calcium from intracellular stores occurs in the presence of halothane. Changes in intracellular calcium concentration ([Ca(2+)](i)) were measured using fluo-3, a fluorescent calcium-sensitive dye and laser scanning confocal microscopy. Halothane, at sub-anesthetic concentrations (14, 28, 40 and 56 microM), increased [Ca(2+)](i) in SN56 cells. This effect remained even when the cells were perfused with medium lacking extracellular calcium, suggesting the involvement of intracellular Ca(2+) sources. SN56 cells responded to ryanodine by increasing [Ca(2+)](i) and this effect was blocked by dantrolene, an inhibitor of Ca(2+)-release from ryanodine-sensitive stores. The effect of halothane was attenuated after the increase in [Ca(2+)](i) induced by ryanodine and it was suppressed by dantrolene, suggesting the participation of ryanodine-sensitive stores. Using cyclopiazonic acid, a Ca(2+)-ATPase inhibitor, we investigated whether the depletion of intracellular Ca(2+) stores interfered with the effect of halothane. Cyclopiazonic acid significantly decreased the increase in [Ca(2+)](i) induced by the volatile anesthetic. It is suggested that sub-anesthetic concentrations of halothane may increase [Ca(2+)](i) by releasing Ca(2+) from intracellular stores in cholinergic cells.
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PMID:Halothane-induced intracellular calcium release in cholinergic cells. 1172 Jul 16

We tested the hypothesis that the mechanism through which cyclic GMP reduces cardiac function is mediated by activation of the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA). Cardiac myocytes were isolated from New Zealand white rabbits (n = 11). Individual ventricular cells were stimulated by electrical field stimulation. The maximal rate of cell shortening and percentage shortening were measured with a video edge detector. Thapsigargin (10(-8) mol/l) was used as a specific inhibitor of SERCA. When 8-bromo-cyclic GMP (8-Br-cGMP, 10(-7, -6, -5) mol/l) was added to cells, the maximal rate of myocyte shortening (R(max), microm/s) and percentage shortening were both decreased in a concentration-dependent manner. R(max) decreased 27% from 117 +/- 12 at baseline to 85.2 +/- 13 when 10(-5) mol/l of 8-Br-cGMP was present, and percent shortening was reduced 28% from 6.0 +/- 0.5 to 4.3 +/- 0.5%. Thapsigargin (10(-8) mol/l) increased the maximal rate of myocyte shortening and percent shortening. Addition of thapsigargin prior to 8-Br-cGMP reduced the negative effects of cGMP on myocyte function. The percent shortening decreased only 11% and R(max) decreased 14% with 10(-5) mol/l 8-Br-cGMP, which was not significant. Cyclopiazonic acid, another SERCA inhibitor, was also used to test whether 8-Br-cGMP reduced myocyte function through SERCA. The results were similar to those when thapsigargin was used. These results indicated that the cyclic GMP-induced reduction in cardiac myocyte function was partially mediated through the action of the sarcoplasmic reticulum Ca(2+)-ATPase.
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PMID:Cyclic GMP-induced reduction in cardiac myocyte function is partially mediated by activation of the sarcoplasmic reticulum Ca(2+)-ATPase. 1180 51

A hypothesis in which intramembrane charge reflects a voltage sensing process allosterically coupled to transitions in ryanodine receptor (RyR)-Ca(2+) release channels as opposed to one driven by release of intracellularly stored Ca(2+) would predict that such charging phenomena should persist in skeletal muscle fibres unable to release stored Ca(2+). Charge movement components were accordingly investigated in intact voltage-clamped amphibian fibres treated with known sarcoplasmic reticular (SR) Ca(2+)-ATPase inhibitors. Cyclopiazonic acid (CPA) pretreatment abolished Ca(2+) transients in fluo-3-loaded fibres following even prolonged applications of caffeine (10 mM) or K(+) (122 mM). Both CPA and thapsigargin (TG) transformed charge movements that included delayed (q(gamma)) "hump" components into simpler decays. However, steady-state charge-voltage characteristics were conserved to values (maximum charge, Q(max) approximately equal to 20-25 nC microF(-1); transition voltage, V* approximately equal to -40 to-50 mV; steepness factor, k approximately equal to 6-9 mV; holding voltage -90 mV) indicating persistent q(gamma) charge. The features of charge inactivation similarly suggested persistent q(beta) and q(gamma) charge contributions in CPA-treated fibres. Perchlorate (8.0 mM) restored the delayed kinetics shown by "on" q(gamma) charge movements, prolonged their "off" decays, conserved both Q(max) and k, yet failed to restore the capacity of such CPA-treated fibres for Ca(2+) release. Introduction of perchlorate (8.0 mM) or caffeine (0.2 mM) to tetracaine (2.0 mM)-treated fibres, also known to restore q(gamma) charge, similarly failed to restore Ca(2+) transients. Steady-state intramembrane q(gamma) charge thus persists with modified kinetics that can be restored to its normally complex waveform by perchlorate, even in intact muscle fibres unable to release Ca(2+). It is thus unlikely that q(gamma) charge movement is a consequence of SR Ca(2+) release rather than changes in tubular membrane potential.
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PMID:Differential effects of sarcoplasmic reticular Ca(2+)-ATPase inhibition on charge movements and calcium transients in intact amphibian skeletal muscle fibres. 1189 56

Effects of tetrandrine (TET), a bisbenzylisoquinoline alkaloid, on the contractile responses of perfused rat mesenteric arteries to phenylephrine (PE) and caffeine were investigated. TET concentration-dependently (1-30 micro M) attenuated phenylephrine-induced responses but potentiated the contractile responses to caffeine (5-40 mM) in the presence and absence of Ca(2+). Berbamine (BER), a structural analogue of TET, elicited a relatively smaller inhibitory effect on the responses to PE due to Ca(2+) release or Ca(2+) influx. However, both TET and BER elicited a comparable potentiating effect on caffeine-induced contraction. Cyclopiazonic acid (CPA; 10 micro M), a selective sarcoplasmic reticulum Ca(2+)-ATPase pump inhibitor, mimicked the potentiating effect of TET when added 5 min prior to caffeine in Ca(2+)-free medium. However, CPA did not augment and might even inhibit the caffeine-induced response when it was preincubated with the tissue for 25 min prior to the addition of caffeine. We propose that TET elicits differential effects on PE- and caffeine-induced responses in perfused rat mesenteric arterial bed. The inhibitory effect of TET on PE-induced responses is probably due to its direct interactions with alpha-adrenoceptors and PE-sensitive Ca(2+)-channels. The augmentation of caffeine-induced responses by TET, particularly in Ca(2+)-free medium, is likely to be due to its partial inhibition of the sarcoplasmic reticulum Ca(2+)-ATPase pump.
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PMID:Tetrandrine potentiates caffeine-induced contraction but inhibits phenylephrine-induced contraction in perfused rat mesenteric artery. 1244 4

Although evidence suggests that high intracellular calcium activity ([Ca2+]i) inhibits sperm motility, data concerning [Ca2+]i within, or slightly above, the physiological range are sparse, particularly in mammalian sperm. We investigated inhibitors of the sarcoplasmic/endoplasmic reticulum Ca-ATPase (SERCA) and the plasma membrane Ca-ATPase with the objective of increasing the intracellular calcium ion activity in human spermatozoa to study its effect on motility and other functions. Thapsigargin (20 micromol/L) increased [Ca2+]i from 140 +/- 7 nmol/L over an approximately 2-min period to reach a plateau of 530 +/- 84 nmol/L (mean +/- SEM, n = 3, p < 0.05). In sperm suspended in calcium-free medium thapsigargin increased [Ca2+]i from 13 +/- 3.3 to 35 +/- 7.5 nmol/L (p < 0.01), consistent with the release of calcium from intracellular stores. Cyclopiazonic acid (60 micromol/L) caused a transient decrease in [Ca2+]i. Quercetin, (200 micromol/L) caused a rapid increase in [Ca2+]i to 1280 +/- 90 nmol/L, after which [Ca2+]i fell quickly at first but then more slowly. Thapsigargin (20 micromol/L) caused approximately 70% of sperm to acrosome react in < or = 5 min, but once acrosome reacted, many sperm died over the next 30 min. Lower concentrations of thapsigargin caused fewer acrosome reactions but were less toxic. Both thapsigargin and quercetin caused rapid dose-dependent decreases in sperm motility. The results are consistent with high [Ca2+]i in the range observed in caput epididymal or cryopreserved spermatozoa inhibiting motility, but might be confounded by other events following the acrosome reaction.
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PMID:Effects of Ca-ATPase inhibitors on the intracellular calcium activity and motility of human spermatozoa. 1463 22

Ca(2)(+) transients elicited by action potentials were measured using MagFluo-4, at 20-22 degrees C, in intact muscle fibres enzymatically dissociated from mice of different ages (7, 10, 15 and 42 days). The rise time of the transient (time from 10 to 90% of the peak) was 2.4 and 1.1 ms in fibres of 7- and 42-day-old mice, respectively. The decay of the transient was described by a double exponential function, with time constants of 1.8 and 16.4 ms in adult, and of 4.6 and 105 ms in 7-day-old animals. The fractional recovery of the transient peak amplitude after 10 ms, F(2(10))/F(1), determined using twin pulses, was 0.53 for adult fibres and ranged between 0.03 and 0.60 in fibres of 7-day-old animals This large variance may indicate differences in the extent of inactivation of Ca(2)(+) release, possibly related to the difference in ryanodine receptor composition between young and old fibres. At the 7 and 10 day stages, fibres responded to Ca(2)(+)-free solutions with a larger decrease in the transient peak amplitude (25% versus 11% in adult fibres), possibly indicating a contribution of Ca(2)(+) influx to the Ca(2)(+) transient in younger animals. Cyclopiazonic acid (1 mum), an inhibitor of the sarcoplasmic reticulum (SR) Ca(2)(+)-ATPase, abolished the Ca(2)(+) transient decay in fibres of 7- and 10-day-old animals and significantly reduced its rate in older animals. Analysis of the transients with a Ca(2)(+) removal model showed that the results are consistent with a larger relative contribution of the SR Ca(2)(+) pump and a lower expression of myoplasmic Ca(2)(+) buffers in fibres of young versus old animals.
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PMID:Calcium transients in developing mouse skeletal muscle fibres. 1573 Nov 92

Manganese (Mn) is a required co-factor for many ubiquitous enzymes; however, chronic Mn overexposure can cause manganism, a parkinsonian-like syndrome. Previous studies showed Mn influx into brain is carrier-mediated, though the putative carrier(s) were not established. Studies conducted with cultured bovine brain microvascular endothelial cells (bBMECs), which comprise the blood-brain barrier, revealed (54)Mn (II) uptake positively correlated with pH, was temperature-dependent, and was sodium- and energy-independent. Brain (54)Mn uptake correlated inversely with calcium (Ca) concentration, but (45)Ca uptake was unaltered by high Mn concentration. Lanthanum (La), a non-selective inhibitor of several Ca channel types, as well as verapamil and amiloride, inhibitors of voltage-operated Ca channels, failed to inhibit Mn uptake into cells. Nickel (Ni), another non-selective inhibitor of several Ca channel types, inhibited Mn and Ca uptake into cells by 88 and 85%, respectively. Cyclopiazonic acid (CPA) and thapsigargin, which activate store-operated calcium channels (SOCCs), increased (54)Mn and (45)Ca uptake into cultured bBMECs. In situ brain perfusion studies were conducted in adult, male Sprague-Dawley rats to verify the cell culture results. Both nickel and verapamil produced a non-significant decrease in Mn and Ca influx. Lanthanum significantly increased Mn influx to 675 and 450% of control in parietal cortex and caudate, respectively, while producing no significant effect on Ca influx. Vanadate, which inhibits Ca-ATPase, inhibited Mn uptake into cultured blood-brain barrier cells, but not into perfused rat brain. Overall these results suggest that both Ca-dependent and Ca-independent mechanisms play a role in brain Mn influx. This work provides evidence that store-operated Ca channels, as well as another mechanism at the blood-brain barrier, likely play a role in carrier-mediated Mn influx into the brain.
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PMID:Manganese distribution across the blood-brain barrier. IV. Evidence for brain influx through store-operated calcium channels. 1593 2

Ca(2+)-ATPases keep cytoplasmic [Ca(2+)] low by pumping Ca(2+) into intracellular compartments or out of the cell. The transport properties of Ca(2+)-pumping ATPases from carrot (Daucus carota cv Danvers) tissue culture cells were studied. ATP-dependent Ca(2+) transport in vesicles that comigrated with an endoplasmic reticulum marker, was stimulated three- to fourfold by calmodulin. Cyclopiazonic acid (a specific inhibitor of the sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase) partially inhibited oxalate-stimulated Ca(2+) transport activity; however, it had no effect on calmodulin-stimulated Ca(2+) uptake driven by ATP or GTP. The results would suggest the presence of two types of Ca(2+)-ATPases, an endoplasmic reticulum- and a plasma membrane-type. Interestingly, incubation of membranes with [gamma(32)P]ATP resulted in the formation of a single acyl [(32)P]phosphoprotein of 120 kilodaltons. Formation of this phosphoprotein was dependent on Ca(2+), but independent of Mg(2+). Its enhancement by La(3+) is characteristic of a phosphorylated enzyme intermediate of a plasma membrane-type Ca-ATPase. Calmodulin stimulated Ca(2+) transport was decreased by W-7 (a calmodulin antagonist), ML-7 (myosin light chain kinase inhibitor) or thyroxine. Acidic phospholipids, like phosphatidylserine, stimulated Ca(2+) transport, similar to their effect on the erythrocyte plasma membrane Ca(2+)-ATPase. These results would indicate that the calmodulin-stimulated Ca(2+) transport originated in large part from a plasma membrane-type Ca(2+) pump of 120 kilodaltons. The possibility of calmodulin-stimulated Ca(2+)-ATPases on endomembranes, such as the endoplasmic reticulum and secretory vesicles, as well as the plasma membrane is suggested.
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PMID:Calcium-pumping ATPases in vesicles from carrot cells : stimulation by calmodulin or phosphatidylserine, and formation of a 120 kilodalton phosphoenzyme. 1666 81

The plant pathogenic fungus Aspergillus flavus produces several types of mycotoxins. The most well known are the carcinogenic compounds called aflatoxins. In addition, A. flavus produces cyclopiazonic acid and aflatrem mycotoxins, contributing to the toxicity of A. flavus infected crops. Cyclopiazonic acid is a specific inhibitor of calcium-dependent ATPase in the sarcoplasmic reticulum that results in altered cellular Ca++ levels. Aflatrem is a potent tremorgenic mycotoxin known to lead to neurological disorders. Previously we showed that a gene called veA controls aflatoxin and sclerotial production in A. parasiticus. In this study in A. flavus, we show that the veA homolog in A. flavus not only is necessary for the production of aflatoxins B1 and B2 and sclerotia, but also regulates the synthesis of the mycotoxins cyclopiazonic acid and aflatrem. The A. flavus DeltaveA mutant was completely blocked in the production of aflatrem and showed greater than twofold decrease in cyclopiazonic acid production. The genes involved in the synthesis of cyclopiazonic acid are unknown; however, the aflatrem gene cluster has been characterized. Northern hybridization analysis showed that veA is required for expression of the A. flavus aflatrem genes atmC, atmG, and atmM. This is the first report of a regulatory gene governing the production of cyclopiazonic acid and aflatrem mycotoxins.
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PMID:Production of cyclopiazonic acid, aflatrem, and aflatoxin by Aspergillus flavus is regulated by veA, a gene necessary for sclerotial formation. 1698 22


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