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)

Recent findings on endothelin, an endothelium-derived vasoconstrictor substance and endogenous digitalislike Na+, K+-ATPase inhibitor (s) obtained from animal and clinical experiments are reviewed. Endothelin is one of the most potent vasoconstrictive substances ever found; the pressor responses last for more than one hour after the bolus injection in rats. Because the pressor responses have not been attenuated by any known receptor-antagonists, the vasoconstriction is mediated by the endothelin receptors. Since messenger RNA for endothelin increases with thrombin, it may be involved in the damages of blood vessels. Radioimmunoassay for endothelin revealed that immunoreactive endothelin is increased in plasma of patients with chronic renal failure. Therefore, the plasma level of endothelin can be an index for some circulatory disorders. Since the Na+, K+-ATPase inhibitor cross-reacts with antidigoxin and antiouabain antibody, it is called a digitalis-like substance. We have demonstrated that cells containing the immunoreactive-substance to antidigoxin and antiouabain antibodies are restricted in the paraventricular and supraoptic nucleus of the hypothalamus, and that the plasma digoxinlike immunoreactivity increases with intracerebroventricular and intravenous infusions of hypertonic saline in rats. Because plasma concentrations of the immunoreactive substance significantly correlate with blood pressure, the substance seems to be involved in hypertension associated with excess intake of sodium salt.
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PMID:[Endothelin and endogenous digitalis-like substance in cardiovascular regulation: a review]. 268 97

Plasma from insulin-dependent diabetics shows an increased ability to specifically activate the (Na-K)ATPase from different sources. Several protease inhibitors like phenyl methyl sulfonyl fluoride, trypsin inhibitor, antithrombin III and aprotinin, produced a significant dose-dependent inhibition of the stimulatory effect produced by a 1/100 final dilution of plasma on the beef heart (Na-K)ATPase activity. Serine proteases employed at scalar concentrations in the ATPase medium gave a dose-dependent stimulation of the enzyme activity as did diabetic plasma. The maximum percent stimulation of the (Na-K)ATPase activity (about 60%) was reached by 0.56 microgram/ml of thrombin, 0.50 microgram/ml of kallikrein and 0.55 microgram/ml of trypsin. The protease-induced ATPase stimulation was significantly reduced by antithrombin III, trypsin inhibitor and by aprotinin. A partial purification of the activating plasma factor was obtained by eluting plasma on a heparin-Sepharose column. Two (Na-K)ATPase stimulating fractions were found, which eluted with 1.0 and 3.0 mol/l NaCl, respectively. Half-maximal stimulation of the enzyme occurred with 3.4 micrograms/ml proteins of fraction 1.0 mol/l and with 45 ng/ml proteins of fraction 3.0 mol/l, this last representing the most purified plasma fraction (about 8890-fold purification). The proteolytic activity of both plasma and purified plasma fractions was tested on Tos-Arg-OMe substrate which was hydrolyzed to a much higher degree by the most purified plasma fraction. Like the (Na-K)ATPase stimulation, the esterolytic activity was inhibited by protease inhibitors, the most effective to this regard being antithrombin.
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PMID:Identification and partial purification of a (Na-K)ATPase stimulating serine protease from plasma of insulin-dependent diabetics. 283 59

Thrombin exhibited diverse effects on mouse 3T3 fibroblasts. It (a) decreased cAMP in the cell suspension, (b) inhibited adenylate cyclase in the Lubrol-permeabilized cell suspension in a GTP-dependent manner, increased releases of (c) arachidonic acid and (d) inositol from the cell monolayer prelabeled with these labeled compounds, (e) increased 45Ca2+ uptake into the cell monolayer, and (f) increased 86Rb+ uptake into the cell monolayer in a ouabain-sensitive manner. Most of the effects were reproduced by bradykinin, platelet-activating factor, and angiotensin II. The receptors for these agonists are thus likely to be linked to three separate effector systems: the adenylate cyclase inhibition, the phosphoinositide breakdown leading to Ca2+ mobilization and phospholipase A2 activation, and the Na,K-ATPase activation. Among the effects of these agonists, (a), (b), (c), and (e) were abolished, but (d) and (f) were not, by prior treatment of the cells with islet-activating protein (IAP), pertussis toxin, which ADP-ribosylates the Mr = 41,000 protein, the alpha-subunit of the inhibitory guanine nucleotide regulatory protein (Ni), thereby abolishing receptor-mediated inhibition of adenylate cyclase. The effects (a), (c), (d), and (e) of thrombin, but not (b), were mimicked by A23187, a calcium ionophore. The effects of A23187, in contrast to those of receptor agonists, were not affected by the treatment of cells with IAP. Thus, the IAP substrate, the alpha-subunit of Ni, or the protein alike, may play an additional role in signal transduction arising from the Ca2+-mobilizing receptors, probably mediating process(es) distal to phosphoinositide breakdown and proximal to Ca2+ gating.
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PMID:Receptor-mediated inhibition of adenylate cyclase and stimulation of arachidonic acid release in 3T3 fibroblasts. Selective susceptibility to islet-activating protein, pertussis toxin. 286 Jan 11

We have characterized various structural and enzymatic properties of the (68K-30K)-S-1 derivative obtained by thrombic cleavage [Chaussepied, P., Mornet, D., Audemard, E., Derancourt, J., & Kassab, R. (1986) Biochemistry (preceding paper in this issue)]. The far-ultraviolet CD spectra and thiol reactivity measurements indicated an unchanged overall polypeptide conformation of the enzyme whereas the CD spectra in the near-ultraviolet region suggested a local change in the environments of phenylalanine side chains; the latter finding was rationalized by considering the existence of about five of these amino acids in the vicinity of the cleavage sites. When the binding of Mg2+-ATP and Mg2+-ADP to the derivative was assessed by CD spectroscopy, distinct spectra were obtained with the two nucleotides as with native subfragment 1 (S-1), but some spectral features were unique to the nicked S-1. Stern-Volmer fluorescence quenching studies using acrylamide and the analogues 1,N6-ethenoadenosine 5'-triphosphate and 1,N6-ethenoadenosine 5'-diphosphate indicated that the complexes formed with the modified S-1 have a solute quencher accessibility close to that observed for the complexes with the normal S-1. However, in contrast to the parent enzyme, the thrombin-cut S-1 was unable to bind irreversibly Mg2+-ATP, nor did it form a stable Mg2+-ADP-sodium vanadate complex or achieve the entrapping of Mg2+-ADP after cross-linking of SH1 and SH2 with N,N'-p-phenylenedimaleimide. Additionally, the amplitude of the Pi burst was very low, indicating that the inactivation of the proteolyzed S-1 was linked to the suppression of the hydrolysis step in the ATPase cycle.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alteration of the ATP hydrolysis and actin binding properties of thrombin-cut myosin subfragment 1. 293 24

Ouabain, a digitalis glycoside and an inhibitor of the Mg2+-dependent Na+-K+ ATPase, was used to probe the role of intracellular Na+ levels in the regulation of platelet reactivity. Platelets preincubated with 10 to 150 microM ouabain exhibited a potentiated aggregation response to collagen (14.4 to 180 micrograms/mL), ADP (4 to 12 microM) and thrombin (0.03 to 0.10 unit/mL). Ouabain markedly decreased the time interval between addition of collagen and the onset of shape change. At submaximal concentrations of collagen, thrombin and ADP, preincubation with ouabain increased the rate and amplitude of the aggregation response. Irreversible aggregation was achieved in ouabain-treated platelets by using concentrations of ADP which induced only reversible aggregation in the absence of ouabain. In addition, chelation of extracellular calcium with EGTA or EDTA (2 mM) failed to block reactivity to collagen, ADP or thrombin in ouabain-treated platelets. These results suggest that ouabain induces a "preactivation state" in platelets, perhaps via modulation of intracellular Na+ levels.
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PMID:Ouabain affects platelet reactivity as measured in vitro. 311 Oct 4

Using the thrombin-cut [68-30 kilodalton (kDa)] myosin subfragment 1 (S-1) whose heavy chain has been selectively split within the central 50-kDa region, at Lys-560, with concomitant specific alterations of the ATPase and actin binding properties [Chaussepied, P., Mornet, D., Audemard, E., Derancourt, J., & Kassab, R. (1986) Biochemistry 25, 1134-1140; Chaussepied, P., Mornet, D., Barman, T., Travers, F., & Kassab, R. (1986) Biochemistry 25, 1141-1149], we have isolated and renatured the COOH-terminal 30-kDa fragment associated with the alkali light chains by the procedure recently described [Chaussepied, P., Mornet, D., Audemard, E., Kassab, R., Goodearl, J., Levine, B., & Trayer, I. P. (1986) Biochemistry 25, 4540-4547]. The 30-kDa peptide preparation was found to exhibit a crucial feature of the native S-1; namely, it interacts with F-actin in an adenosine 5'-triphosphate (ATP)-dependent manner. Studies by ultracentrifugation, turbidity measurements, and chemical cross-linking experiments showed that the acto-30-kDa peptide complex was dissociated almost completely by the gamma-phosphoryl group containing ligands ATP, 5'-adenylyl imidodiphosphate, and pyrophosphate, to a lesser extent by ADP, and not at all by AMP and inorganic phosphate. The maximal dissociating effect is operating with the thrombic 30-kDa entity, whereas the 22-kDa fragment produced by staphylococcal protease is only slightly dissociated. In contrast, the tryptic 20-kDa fragment binds irreversibly to actin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Identification of polyphosphate recognition sites communicating with actin sites on the skeletal myosin subfragment 1 heavy chain. 379 May 30

A new antiaggregating chemical, alpha-(p-(fluoren-9-ylidenemethyl)phenyl)-2-piperidineethanol (RMI 10,393), designated FYPE, was found to be an effective inhibitor of platelet aggregation induced by adenosine diphosphate (ADP), thrombin, collagen, or epinephrine. Effects of the antiaggregant on platelets were concentration dependent. Aggregation was prevented by low concentrations of FYPE that produced in the platelet only minor ultrastructural changes consisting of loss of microtubules and of discoid shape. Low levels of FYPE that prevented platelet aggregation had no effect on platelet ATPase activities but did alter clot retraction, the thrombin-induced shift in electrophoretic mobility and platelet cholinesterase activity. Market decrease in ADP release and increase in adenyl cyclase activity were produced by low levels of FYPE. This study provides a model for evaluation of platelet antiaggregating compounds in vitro.
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PMID:Effect of a new antiaggregating chemical on the structure and function of the human platelet. 425 15

Stimulation of amiloride-sensitive sodium (Na+) influx and the subsequent activation of NA+, K+-ATPase by serum or growth factors have been implicated as early events leading to initiation of cell proliferation. We recently demonstrated that amiloride inhibits thrombin-initiated DNA synthesis not by inhibiting an early event occurring during the first 8 hr, but rather by inhibiting some later event 8 to 12 hr after thrombin addition. To further probe the relationship between stimulation of ion influx and initiation of cell proliferation, human alpha-thrombin was converted to gamma-thrombin, nitro-alpha-thrombin, and diisopropylphospho (DIP)-alpha-thrombin. These derivatives retain either the capacity to bind cell surface alpha-thrombin receptors or thrombin esterase activity, but they do not initiate DNA synthesis. At low concentrations of alpha-thrombin or the various thrombin derivatives, only alpha-thrombin stimulates 86Rb+ influx, suggesting a correlation between stimulation of influx and the ability of these derivatives to initiate DNA synthesis. Concentrations of a DIP-alpha-thrombin that saturate the alpha-thrombin receptors (up to 2 micrograms/ml) do not stimulate either the early or late influx of 86Rb+, indicating that DIP-alpha-thrombin binding alone is not sufficient to stimulate ion fluxes. High concentrations of either gamma-thrombin or nitro-alpha-thrombin, however, stimulate both early and late 86RB+ uptake but do not initiate DNA synthesis. These results demonstrate that events leading to both the early and late stimulation of 86Rb+ influx by themselves are not sufficient to initiate cell proliferation. Thus, initiation may require a combination of events that can be independently regulated by different transmembrane signals.
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PMID:Initiation of DNA synthesis by human thrombin: relationships between receptor binding, enzymic activity, and stimulation of 86Rb+ influx. 608 80

Fragments of rabbit skeletal muscle Ca2+-binding subunit of troponin (TnC), obtained by cleavage with trypsin, thrombin, and CNBr, were tested for their ability to form binary and ternary complexes with ATPase inhibitory subunit (TnI) and tropomyosin-binding subunit (TnT) and their ability to replace TnC in reversing TnI inhibition of actomyosin ATPase activity. Three regions of TnC were found to be involved in interaction with TnI. Regions near Ca2+-binding sites II and III require Ca2+ for the interaction, while a third region near Ca2+-binding site IV binds TnI whether or not Ca2+ is present. The TnT binding site has been localized in the NH2-terminal half of TnC. Several of the TnC fragments form soluble ternary complexes with TnI and TnT. Fragments that contain amino acid residues 89-100 and at least one pair of Ca2+-binding sites are able to reverse the TnI inhibition of actomyosin ATPase activity, which exhibits the same [Ca2+]1/2 regardless of which of the Ca2+-binding sites are present in the fragment.
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PMID:Proteolytic fragments of troponin C. Interactions with the other troponin subunits and biological activity. 645 9

Amiloride, a Na+ influx inhibitor, has been shown to inhibit initiation of DNA synthesis by thrombin in mouse embryo fibroblast-like cells. Long exposures (24 hr) to high concentrations of amiloride inhibited incorporation of thymidine into the DNA of both thrombin-stimulated and nonstimulated cells, suggesting that this inhibition might not be specific for thrombin-initiated DNA synthesis. Fluorescence microscopy and spectrofluorimetry showed that amiloride was internalized with an apparent mitochondrial association and that the internalized amiloride was readily released from the cells after removing amiloride from the medium. Based on this reversibility, cells were exposed to amiloride for short periods of time during thrombin treatment to determine the temporal relationship between any amiloride-sensitive event(s) and initiation of DNA synthesis. The presence of amiloride (100 microM) during a 12-hr exposure to thrombin did not block thrombin-initiated DNA synthesis or cell division but did delay the onset of DNA synthesis and the peak of thymidine incorporation into DNA by approximately 3 hr, suggesting that early initiation events might proceed in the presence of amiloride. 86Rb+ transport studies demonstrated that in this system ouabain-sensitive K+ uptake via the Na, K-ATPase was stimulated by thrombin during both an early and a late period. This stimulation was amiloride-sensitive under the same conditions used for growth experiments, suggesting that amiloride was inhibiting thrombin-stimulated Na+ transport in this system. Additional experiments showed that exposing cells to amiloride only during the first 8 hr after thrombin addition did not inhibit initiation. The presence of amiloride from 8-12 hr after thrombin addition maximally inhibited thrombin-stimulated DNA synthesis. Together these results demonstrate that amiloride inhibits thrombin-initiated DNA synthesis not by inhibiting an early event occurring during the first 8 hr, but rather by inhibiting some later event 8-12 hr after thrombin addition.
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PMID:Demonstration of a late amiloride-sensitive event as a necessary step in initiation of DNA synthesis by thrombin. 663 Mar 2


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