Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20020 (adenosine triphosphatase)
 3,299 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The weakly basic, lipophilic Ca++ antagonists perhexiline and cinnarizine have been compared with the calmodulin inhibitor W-7 and the cardiotonics Vardax and APP-201-533 for the ability to modulate Ca++-dependent contractile protein interactions directly, as well as Ca++-calmodulin-mediated myosin light chain phosphorylation, in arterial actomyosin or cardiac myofibrils. Both perhexiline and cinnarizine inhibited arterial myosin P-light chain phosphorylation and superprecipitation of arterial actomyosin over the concentration range of 10 to 200 microM. Concomitant inhibition of arterial superprecipitation and phosphorylation by perhexiline (IC50 = 33 microM) and cinnarizine (IC50 = 60 microM) was similar to W-7 (IC50 = 35 microM), and was characterized by a rightward shift in the pCa superprecipitation and pCa-light chain phosphorylation relationships, depressed maximum activity and attenuation by 2 microM exogenous calmodulin. However, whereas inhibition of superprecipitation and P-light chain phosphorylation by W-7 was equal at different Mg++ concentrations, relatively greater inhibition with perhexiline and less inhibition with cinnarizine was apparent as the free Mg++ concentration was lowered. In cardiac myofibrils prepared from both bovine and canine ventricles, perhexiline stimulated Mg-adenosine triphosphatase (ATPase) activity and cinnarizine was without effect, whereas W-7 significantly depressed ATPase activity. Perhexiline was 10-fold more potent and 3-fold more efficacious than either Vardax or APP-201-533 in canine cardiac myofibrils. Whereas APP-201-533 increased Ca++ sensitivity and maximum ATPase activity (Vmax), perhexiline increased Ca++ sensitivity, but not Vmax, and W-7 depressed both parameters.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of the calcium antagonists perhexiline and cinnarizine on vascular and cardiac contractile protein function. 316 16

Active Na+ and Ca2+ transports by sarcolemmal vesicles from young spontaneously hypertensive rats (SHR) and their normotensive controls (WKY) were compared. The effects of the calmodulin and the calcium antagonist nifedipine on Ca2+ binding ATP-dependent accumulation of Ca2+ were studied at free Ca2+ concentrations of 2.10(-8)M and 4.10(-7)M. 2.10(-7)M calmodulin stimulated Ca2+ binding to SHR membranes up to a level equivalent to that in WKY, whereas it enhanced active Ca2+ transport more in WKY than in SHR, thus suppressing the difference between the two substrains. At a 2.10(-8)M free Ca2+ concentration low concentrations of nifedipine (10(-7) to 10(-6)M) induced an increases in ATP-dependent Ca2+ transport by SHR vesicles. Inhibition of NA+, K+-adenosine triphosphatase activity by ouabain was also studied. Na+, K+ATPase activity in SHR membranes was double that in membranes from WKY (22.1 +/- 2.8 v.s. 11.3 +/- 1.1. mumole Pi/h/mg protein). These differences, observed on 3 week-old rats, before a significant rise blood pressure, may reflect genetic characteristics of these hypertensive-prone rats.
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PMID:[Active calcium and sodium transport by cardiac plasma membranes in the genetically hypertensive rat]. 609 37

An ATP-dependent transport system which is active at concentrations of free Ca2+ in the submicromolar range has been identified in adipocyte plasma membranes. The system appears to represent the functional component of the high affinity insulin-sensitive calcium-stimulated, magnesium-dependent adenosine triphosphatase preveiously described in the same preparation (Pershadsingh, H. A., and McDonald, J. M. (1979) Nature 281, 495-497). This ATP-dependent Ca2+ transport pump was stimulated approximately 3-fold by the Ca2+-dependent regulatory protein, calmodulin. This effect was confined to the plasma membrane since a similar effect was undetectable in the fraction enriched in endoplasmic reticulum. Calmodulin stimulation was dose-dependent but saturable with half-maximal activation occurring at 0.72 microgram/ml (43 nM). Calmodulin appeared to stimulate the system primarily by decreasing the apparent half-maximal saturation constant for free Ca2+ from 0.20 +/- 0.04 microM to 0.07 +/- 0.01 microM (n = 3). The Hill coefficient increased from 1.6 +/- 0.2 to 3.2 +/- 0.6 (n = 3), thus showing an increased positive cooperativity which allows the pump to be activated by an exceedingly narrow Ca2+ threshold in the presence of calmodulin. The calmodulin stimulation of the plasma membrane Ca2+ extrusion pump in adipocytes, working in opposition to metabolic signals which increase cytoplasmic Ca2+, could constitute a self-regulating negative feedback device for maintaining a low steady state level of intracellular Ca2+. This feedback system may be of critical importance in regulation of cellular metabolism by insulin.
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PMID:Calmodulin-sensitive ATP-dependent Ca2+ transport across adipocyte plasma membranes. 610 20

A Mg-dependent adenosine triphosphatase (ATPase) activated by submicromolar free Ca2+ was identified in detergent-dispersed rat liver plasma membranes after fractionation by concanavalin A-Ultrogel chromatography. Further resolution by DE-52 chromatography resulted in the separation of an activator from the enzyme. The activator, although sensitive to trypsin hydrolysis, was distinct from calmodulin for it was degraded by boiling for 2 min, and its action was not sensitive to trifluoperazine; in addition, calmodulin at concentrations ranging from 0.25 ng-25 micrograms/assay had no effect on enzyme activity. Ca2+ activation followed a cooperative mechanism (nH = 1.4), half-maximal activation occurring at 13 +/- 5 nM free Ca2+. ATP, ITP, GTP, CTP, UPT, and ADP displayed similar affinities for the enzyme; K0.5 for ATP was 21+/- 9 microM. However, the highest hydrolysis rate (20 mumol of Pi/mg of protein/10 min) was observed at 0.25 mM ATP. For all the substrates tested kinetic studies indicated that two interacting catalytic sites were involved. Half-maximal activity of the enzyme required less than 12 microM total Mg2+. This low requirement for Mg2+ of the high affinity (Ca2+-Mg2+)ATPase was probably the major kinetic difference between this activity and the nonspecific (Ca2+ or Mg2+)ATPase. In fact, definition of new assay conditions, i.e. a low ATP concentration (0.25 mM) and the absence of added Mg2+, allowed us to reveal the (Ca2+-Mg2+)ATPase activity in native rat liver plasma membranes. This enzyme belongs to the class of plasma membrane (Ca2+-Mg2+)ATPases dependent on submicromolar free Ca2+ probably responsible for extrusion of intracellular Ca2+.
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PMID:A high affinity calcium-stimulated magnesium-dependent ATPase in rat liver plasma membranes. Dependence of an endogenous protein activator distinct from calmodulin. 611 12

An isolated plasma membrane fraction from bovine thyroid glands contained a Ca2+-stimulated, Mg2+-dependent adenosine triphosphatase ((Ca2+ + Mg2+)-ATPase) activity which was purified in parallel to (Na+ + K+)-ATPase and adenylate cyclase. The (Ca2+ + Mg2+)-ATPase activity was maximally stimulated by approx. 200 microM added calcium in the presence of approx. 200 microM EGTA (69.7 +/- 5.2 nmol/mg protein per min). In EGTA-washed membranes, the enzyme was stimulated by calmodulin and inhibited by trifluoperazine.
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PMID:Ca2+-stimulated, Mg2+-dependent ATPase in bovine thyroid plasma membranes. 612 Jul 20

Rabbits were made reticulocytotic by repeated bleeding or by injection of phenylhydrazine. Up to reticulocyte levels of 70%, the baseline activity of magnesium-dependent calcium-stimulated adenosine triphosphatase ( ( Ca + Mg)-ATPase, EC 3.6.1.3.) of the red cell plasma membrane was not significantly changed. Maximal activity in the presence of calmodulin was significantly reduced, the stimulation by the activator falling from about 350% to about 50%.
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PMID:The (Ca + Mg)-ATPase of reticulocytes. 613 90

A unique cytoplast preparation from Ehrlich ascites tumor cells (G. V. Henius, P. C. Laris, and J. D. Woodburn (1979) Exp. Cell. Res. 121, 337-345), highly enriched in plasma membranes, was employed to characterize the high-affinity plasma membrane calcium-extrusion pump and its associated adenosine triphosphatase (ATPase). An ATP-dependent calcium-transport system which had a high affinity for free calcium (K0.5 = 0.040 +/- 0.005 microM) was identified. Two different calcium-stimulated ATPase activities were detected. One had a low (K0.5 = 136 +/- 10 microM) and the other a high (K0.5 = 0.103 +/- 0.077 microM) affinity for free calcium. The high-affinity enzyme appeared to represent the ubiquitous high-affinity plasma membrane (Ca2+ + Mg2+)-ATPase (calcium-stimulated, magnesium-dependent ATPase) seen in normal cells. Both calcium transport and the (Ca2+ + Mg2+)-ATPase were significantly stimulated by the calcium-dependent regulatory protein calmodulin, especially when endogenous activator was removed by treatment with the calcium chelator ethylene glycol bis(beta-aminoethyl ether) N,N'-tetraacetic acid. Other similarities between calcium transport and the (Ca2+ + Mg2+)-ATPase included an insensitivity to ouabain (0.5 mM), lack of activation by potassium (20 mM), and a requirement for magnesium. These similar properties suggested that the (Ca2+ + Mg2+)-ATPase represents the enzymatic basis of the high-affinity calcium pump. The calcium pump/enzyme system was inhibited by orthovanadate at comparatively high concentrations (calcium transport: K0.5 congruent to 100 microM; (Ca2+ + Mg2+)-ATPase: K0.5 greater than 100 microM). Upon Hill analysis, the tumor cell (Ca2+ + Mg2+)-ATPase failed to exhibit cooperative activation by calcium which is characteristic of the analogous enzyme in the plasma membrane of normal cells.
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PMID:A high-affinity, calmodulin-sensitive (Ca2+ + Mg2+)-ATPase and associated calcium-transport pump in the Ehrlich ascites tumor cell plasma membrane. 613 89

The plasma membrane (Mg2+)-dependent adenosine triphosphatase [Mg2+)-ATPase) from human erythrocytes has been tested for its ability to transport ions. Using a preparation of inside-out vesicles loaded with the pH-sensitive fluorescence probe 1-hydroxypyrene-3,6,8-trisulfonic acid (HPTS), we have demonstrated the absence of proton movement during (Mg2+)-ATPase activity. From the rate of ATP hydrolysis and the passive proton permeability of these vesicles, an upper limit of 0.03 H+ transported per ATP hydrolyzed was calculated. To verify that proton pumping could be detected in this system, the intravesicular pH was monitored during (Ca2+)-dependent adenosine triphosphatase [Ca2+)-ATPase) activity. Proton efflux associated with (Ca2+)-ATPase activity was observed (in agreement with a recent report of proton pumping by a reconstituted erythrocyte (Ca2+)-ATPase (Niggli, V., Sigel, E., Carafoli, E. (1982) J. Biol. Chem. 257:2350-2356] and was shown to be stimulated by calmodulin. The ability of the (Mg2+)-ATPase to pump 28Mg2+, 35SO2-4 and 86Rb+ was also tested, with the results leading to the conclusion that the human erythrocyte enzyme does not function as an ion transport system.
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PMID:The plasma membrane (Mg2+)-dependent adenosine triphosphatase from the human erythrocyte is not an ion pump. 614 24

Properties of (Ca2+ + Mg2+) adenosine triphosphatase (ATPase) in plasma membranes from boar epididymal spermatozoa are described. Enzyme activity is optimum at high pH and has a high affinity for Ca2+. It is not inhibited by the calmodulin antagonist trifluoperazine (TFP), but it is inhibited by low concentrations of Ca2+. Plasma membrane vesicles obtained by hypotonic lysis of intact sperm [mixed inside-out (IOV) and right side-out (ROV) vesicles] transport 45Ca2+ in the presence of oxalate. Similar to the Ca2+-stimulated Mg ATPase activity, transport is unaffected by TFP, but unlike the ATPase, transport is at an optimum rate near neutral pH and is completely inhibited by p-chloromercurphenylsulfonate (pCMS). When plasma membranes are labeled in the presence and absence of Ca2+ and Mg2+ with [gamma-32P]ATP, differences in the intensity of labeling and lability of bound 32P to alkali and hydroxylamine suggest that two polypeptides between 100-120K may be related to a transport ATPase. The addition of TFP at concentrations which stimulate net Ca2+ uptake in intact cells causes intense labeling of a single neutrally charged protein near 68K. These labeling patterns and the properties of (Ca2+ + Mg2+) ATPase identify particular plasma membrane proteins (PMPs) from the complex surface of these cells that may be involved in Ca2+-dependent functions and support the view that calmodulin is not directly involved in the regulation of ATP-driven Ca2+ efflux from boar spermatozoa.
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PMID:Characterization of (Ca2+ + Mg2+) adenosine triphosphatase activity and calcium transport in boar sperm plasma membrane vesicles and their relation to phosphorylation of plasma membrane proteins. 615 5

Inside-out vesicles prepared from human red blood cells took up Ca2+ by an active transport process. Membranes from the same red blood cells displayed Ca2+-activated, Mg2+-dependent adenosine triphosphatase activity. Both the initial rate of Ca2+ transport and the (Ca2+ + Mg2+)-adenosine triphosphatase activity were increased approximately twofold by the calcium binding protein, calmodulin. Activities in the absence of added calmodulin were termed basal activities. Calmodulin-activated Ca2+ transport and adenosine triphosphatase activities could be antagonized in a relatively selective fashion by the phenothiazine tranquilizer drug, trifluoperazine. High concentrations of trifluoperazine also inhibited basal Ca2+ transport and adenosine triphosphatase activity. By contrast, calmodulin binding protein from beef brain selectively antagonized the effect of calmodulin on Ca2+ transport with no inhibition of basal activity. Ruthenium red antagonized calmodulin-activated and basal activity with equal potency. The results demonstrate that although phenothiazines can act as relatively selective antagonists of calmodulin-induced effects, other effects are possible and cannot be ignored. Calmodulin-binding protein may be a useful tool in the analysis of calmodulin functions. Ruthenium red probably interacts with Ca2+ pump adenosine triphosphatase at a site not related to calmodulin.
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PMID:Plasma membrane Ca2+ transport: antagonism by several potential inhibitors. 616 56


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