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)

1 The effect of the Ca(2+)-ATPase inhibitor, cyclopiazonic acid (CPA), was studied on rat thoracic aortic ring preparations. 2 At concentrations above 0.3 microM, CPA induced relaxation in the arteries precontracted with phenylephrine. Removal of the endothelium abolished CPA-induced relaxation. 3 The nitric oxide (NO) synthase inhibitor NG-nitro L-arginine (3-300 microM), the free radical scavenger haemoglobin (0.1-3 microM), the soluble guanylate cyclase inhibitor, LY83583 (0.1-10 microM), each inhibited the endothelium-dependent relaxation to CPA. The potassium channel blocker, glibenclamide (10 microM) and cyclo-oxygenase inhibitor, indomethacin (100 microM for 60 min and then washed out) did not alter the action of CPA. 4 The calmodulin inhibitors calmidazolium (3-10 microM) and W-7 (100 microM) also abolished CPA-induced relaxation. 5 CPA (10 microM) increased guanosine 3':5'-cyclic monophosphate (cyclic GMP) levels in arteries with an intact endothelium, without affecting adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels. 6 The inhibitors of NO synthesis and actions, the calmodulin inhibitor and removal of the endothelium abolished the CPA-stimulated increase in the levels of cyclic GMP. 7 In Ca(2+)-free solution, CPA failed to induce relaxation or to stimulate cyclic GMP production. Relaxation to nitroprusside was not affected under these conditions. 8 These results suggest that CPA can stimulate NO synthesis, possibly by inhibiting a Ca(2+)-ATPase, which replenishes Ca2+ in the intracellular storage sites in endothelial cells. Depletion of the Ca2+ store in the endothelium may then trigger influx of extracellular Ca2+, contributing to an increase in free Ca2+ in the endothelial cells, which activates NO synthase and NO formation.
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PMID:Relaxation of rat thoracic aorta induced by the Ca(2+)-ATPase inhibitor, cyclopiazonic acid, possibly through nitric oxide formation. 751 25

Nitric oxide (NO) is a messenger molecule that is produced from L-arginine by NO synthase (NOS). Some NOS isoforms are present in cells constitutively, whereas others can be induced by cytokines. Recent evidence suggests that NO inhibits intracellular pH regulation by the vacuolar H(+)-adenosinetriphosphatase (ATPase) in macrophages, which contain an inducible form of NOS. The vacuolar H(+)-ATPase is involved in proton secretion in intercalated cells in the collecting duct. We have therefore examined the effect of NO on bafilomycin-sensitive H(+)-ATPase activity in individual cortical collecting ducts (CCD) microdissected from collagenase-treated kidneys of normal rats using a fluorometric microassay. Incubation of CCD with the NO donors, sodium nitroprusside (0.1 and 1 mM) or 3-morpholino-sydnonimine hydrochloride (SIN-1, 30 microM), caused a dose-dependent decrease in H(+)-ATPase activity. Incubation of CCD with lipopolysaccharide (LPS) and interferon-gamma, which induces NOS in macrophages, decreased H(+)-ATPase activity by 85%. This effect was prevented by simultaneous incubation with N omega-nitro-L-arginine, a competitive inhibitor of NOS, indicating that the decrease in H(+)-ATPase activity was caused by NO production. Incubation with 8-bromo-guanosine 3',5'-cyclic monophosphate (cGMP) also inhibited H(+)-ATPase activity, suggesting that NO may exert its effect in the CCD via activation of guanylyl cyclase and production of cGMP. Immunohistochemistry using antibodies to the macrophage-type NOS revealed strong labeling of intercalated cells in the CCD, confirming the presence of NOS in these cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nitric oxide inhibits bafilomycin-sensitive H(+)-ATPase activity in rat cortical collecting duct. 752 55

The ability of putative Ca(2+)-ATPase inhibitor of endoplasmic reticulum (ER), thapsigargin (TG), to induce nitric oxide (NO) synthesis in murine peritoneal macrophages was examined. TG alone had small effect on NO synthesis, whereas TG in combination with LPS markedly increased NO synthesis in a dose dependent manner. This increase in NO synthesis was reflected as increased amount of inducible NO synthase (iNOS) mRNA by Northern blotting. In addition, the ability of TG on NO synthesis could be mimicked by another chemically unrelated inhibitor of Ca(2+)-ATPase, 2,5-DI-(t-butyl)-1, 4-benzohydroquinone (tBuBHQ). Adding EGTA, a calcium chelator, to the incubation medium significantly reduced the ability of macrophages to induce NO synthesis in response to the optimal stimulation of TG or TG plus LPS. These results therefore demonstrate that intracellular Ca2+ pool depletion is linked to the induction of NO synthesis in murine peritoneal macrophages and further suggest that it is also related with interferon-gamma (IFN-gamma)-induced signaling.
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PMID:Intracellular Ca2+ pool depletion is linked to the induction of nitric oxide synthesis in murine peritoneal macrophages. 758 Oct 11

Prior studies indicate that the natriuretic effects of atrial natriuretic peptide (ANP) are due, in part, to an inhibition of the passive movement of sodium ions from tubular lumen through apical cation channels into renal tubular epithelium. The present work demonstrates that ANP also exerts a potent inhibitory effect on the active pumping of sodium ions by renal tubular sodium and potassium-activated adenosine triphosphatase (Na, K-ATPase). This action of ANP is relatively long lasting, is due to a change in enzyme Vmax and is specific for ouabain-sensitive activity. Enzyme modulation occurs with an EC50 for ANP of 0.1 nM, is independent of intracellular [Na+] and is associated with an increase in tissue cyclic GMP (cGMP), but not cyclic AMP (cAMP). Modulation of Na, K-ATPase by ANP is mimicked by 8-bromo-cGMP and okadaic acid (OA) and is blocked by KT 5823, a selective inhibitor of cGMP-dependent protein kinase (PKG), but not by KT 5720, a selective inhibitor of cyclic AMP-dependent protein kinase (PKA), which suggests that the action of ANP on the sodium pump involves cGMP-mediated changes in protein phosphorylation. Regulation of renal Na, K-ATPase activity also occurs with nitric oxide-generating compounds, such as nitroglycerin and sodium nitroprusside (SNP). However, the ability of ANP to modulate Na, K-ATPase does not appear to involve this latter pathway because the effects of ANP on the sodium pump cannot be blocked by either N omega-nitro-L-arginine, an inhibitor of NO synthase, or hemoglobin, which blocks NO through binding.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Atrial natriuretic peptide modulates sodium and potassium-activated adenosine triphosphatase through a mechanism involving cyclic GMP and cyclic GMP-dependent protein kinase. 789 13

1. The purpose of this study was to characterize the effect of NG-nitro-L-arginine methyl ester (L-NAME) on the perfusion rate/pressure relations, and on the pressor responses induced to cirazoline and KCl in isolated, perfused mesenteric arterial beds from normotensive and spontaneously hypertensive rats. 2. The basal perfusion pressure of arterial beds perfused with either physiological salt solution (PSS) or PSS containing 1% polyvinylpyrrolidone increased as the perfusion rate increased. L-NAME, in concentrations up to 100 microM, failed to alter the basal pressure regardless of the perfusion rate and viscosity; however, at 5 microM, it potentiated cirazoline-induced vasoconstriction at each of the perfusion rates. 3. L-NAME but not D-NAME caused a leftward shift of cirazoline concentration-response curves with a marked increase in the maximal response. The potentiating action of L-NAME was abolished in arterial beds perfused with a Ca(2+)-free physiological salt solution and also in beds denuded of endothelium by an infusion of distilled water for 5 min. 4. In endothelium-intact and -denuded preparations, L-NAME potentiated KCl pressor responses; the endothelium-independent potentiation of KCl pressor activity was stereospecific, time-independent and was not prevented by the presence of dexamethasone (0.5 microM) in the perfusion medium. However, L-NAME failed to potentiate vasoconstriction obtained to KCl in arterial beds denervated by cold storage (4-5 degrees C) for 2 days. 5. The absence of K+ in the perfusate did not inhibit the ability of L-NAME to potentiate alpha-adrenoceptor-mediated pressor responses, and nor did L-NAME inhibit KCl-induced vasodilatation in preconstricted arteries. It was thus concluded that L-NAME does not affect Na+/K(+)-ATPase activity. 6. No differences in the potentiating ability of L-NAME on either cirazoline- or KCl-mediated pressor responses were apparent between normotensive Sprague Dawley (SD), Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats.7. Our data thus provide evidence that: the presence of a vasoconstrictor is required for basal nitricoxide (NO) release in the mesenteric arterial bed from either normotensive or spontaneously hypertensive rats; L-NAME causes potentiation of cirazoline- and KCl-induced vasoconstriction respectively by inhibiting endothelial and neuronal NO synthase(s). Furthermore, our data indicate that NO synthase activity is not impaired in the mesenteric arterial bed of spontaneously hypertensive rats.
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PMID:The effects of perfusion rate and NG-nitro-L-arginine methyl ester on cirazoline- and KCl-induced responses in the perfused mesenteric arterial bed of rats. 791 52

Studies were designed to determine the extent of the involvement of endothelium-derived relaxing factor(s) other than nitric oxide (NO) in vascular relaxation in response to acetylcholine (ACh) in the rabbit renal artery. ACh (10(-9)-10(-6) M) induced concentration-dependent relaxation of isolated endothelium-intact arterial rings preconstricted with noradrenaline. NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthase, partly inhibited the ACh-induced endothelium-dependent relaxation, whereas it almost completely abolished the production of cyclic-3', 5'-guanosine monophosphate (cGMP) in these rings in response to ACh. Methylene blue, an inhibitor of guanylate cyclase, had an essentially similar effect to L-NAME on the relaxation. Indomethacin, an inhibitor of cyclooxygenase, had no effect. High concentrations of potassium chloride (to inhibit endothelium-dependent hyperpolarization), tetraethylammonium (TEA) or 4-aminopyridine (4-AP), a voltage-dependent or Ca(2+)-dependent K+ channel blocker, partly inhibited the relaxation while, in contrast, glibenclamide, an ATP-sensitive K+ channel blocker, had no effect. Ouabain, an inhibitor of Na+, K(+)-ATPase, also partly inhibited the ACh-induced relaxation, especially the higher concentration effect. Application of L-NAME together with ouabain, TEA, or a high concentration of potassium chloride completely abolished the relaxation. These results suggest that ACh-induced endothelium-dependent relaxation in the rabbit renal artery is mediated by NO, and by an other factor(s), which relaxes the vascular smooth muscle through opening K+ channels other than ATP-sensitive ones, and/or through the activation of a Na+, K(+)-pump.
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PMID:NG-nitro-L-arginine-resistant endothelium-dependent relaxation induced by acetylcholine in the rabbit renal artery. 804 Dec 28

Thapsigargin induced endothelium-dependent relaxation and cGMP production in rat thoracic aorta, and these effects were inhibited by nitric oxide (NO) pathway inhibitors, a calmodulin inhibitor and removal of Ca2+, suggesting that NO is involved in the thapsigargin-induced relaxation. Thapsigargin may deplete Ca2+ stores in the endothelial cells by inhibiting the Ca(2+)-ATPase, a Ca2+ pump, which in turn triggers influx of extracellular Ca2+, leading to activation of constitutive NO synthase and resultant NO generation. The NO thus formed may activate soluble guanylate cyclase to produce cGMP in the vascular smooth muscle.
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PMID:Thapsigargin, a Ca(2+)-ATPase inhibitor, relaxes rat aorta via nitric oxide formation. 811 11

An endothelium-derived factor with the properties of nitric oxide (NO) has recently been implicated in the regulation of basal Na(+)-K(+)-adenosinetriphosphatase (ATPase) activity in vascular smooth muscle. To determine whether this factor also plays a role in the stimulation of ouabain-sensitive (OS) 86Rb uptake by specific agonists, studies were carried out using rabbit aortic rings. In endothelium-intact rings incubated for 3 h with Krebs-Henseleit solution containing 5.5 mM glucose, endothelin (ET) caused a concentration-dependent increase in OS 86Rb uptake (maximal increase = 205%, with 100 nM ET). Incubation with phenylephrine (Phe; 0.1 and 1 microM) or phorbol 12,13-dibutyrate (PDBu; 0.1 microM), under the same conditions, increased OS 86Rb uptake by 128, 144, and 140%, respectively. Removal of endothelium before incubation decreased the ability of ET to stimulate OS 86Rb uptake by 38-45%, but it did not diminish the stimulation of OS 86Rb uptake by Phe or PDBu. An increase in the concentration of glucose from 5.5 to 44 mM diminished ET-stimulated OS 86Rb uptake by 50% in endothelium-intact rings but had no effect on Phe- or PDBu-induced increases in OS 86Rb uptake. Addition of the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA; 0.3 mM) to the medium decreased ET-stimulated OS 86Rb uptake by 40%. Guanosine 3',5'-cyclic monophophate (cGMP) formation in endothelium-intact rings was also increased (65%) by ET but not by Phe or PDBu. The increase in cGMP by ET was totally inhibited by L-NMMA or endothelium denudation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of endothelium-derived nitric oxide in stimulation of Na(+)-K(+)-ATPase activity by endothelin in rabbit aorta. 814 59

The authors tested the postulate that ouabain releases nitric oxide (NO) from the vascular endothelium of porcine carotid arteries (PCAs) with the technique of perfusion-superfusion bioassay, in which the perfused PCA with endothelium served as the source of NO and superfused left circumflex coronary artery (CMFX) rings with rubbed endothelium served as the bioassay tissue. Selective exposure of the PCA to ouabain (10 microM) enhanced the basal release of NO but did not affect bradykinin-stimulated (BK; 0.1-100 picomoles) release of NO. The effect of ouabain on basal release of NO from PCA persisted after pretreatment of either PCA or circumflex coronary artery with propranolol (1 microM); ibuprofen (1 microM); and hydrocortisone (10 microM). Finally, selective pretreatment of the PCA with L-NG-monomethylarginine (LNMMA; 100 microM) to inhibit 1-arginine-derived NO synthesis inhibited the relaxation of the circumflex coronary artery to basal, BK, and ouabain-stimulated effluent. Since a nonspecific increase in intracellular calcium ion will enhance both basal and agonist-induced release of NO, the authors conclude that a ouabain-sensitive ATPase is involved in basal release of NO from the endothelium of the PCA. Alternatively, ouabain may act on an isozyme of NO synthase in the vascular endothelium. Speculatively, ouabain-induced stimulation of NO release from vascular endothelium may contribute to the beneficial effect of ouabain in congestive heart failure.
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PMID:Ouabain enhances basal release of nitric oxide from carotid artery. 838 25

Because the role of intracellular Ca2+ in the two-signal process for the induction of nitric oxide (NO) synthesis is controversial, this study was undertaken to examine the role of Ca2+ in the transcriptional regulation of inducible NO synthase (iNOS) in murine peritoneal macrophages. Treatment of the cells with thapsigargin (TG) or 2,5-di-(t-butyl)-1,4-benzodihydroquinone (tBuBHQ), which are the specific and potent Ca(2+)-ATPase inhibitors of endoplasmic reticulum (ER), showed modest effects on tumoricidal function, whereas TG or tBuBHQ in combination with interferon-gamma (IFN-gamma) or lipopolysaccharide (LPS) showed marked effects on tumoricidal function of the cells. The tumoricidal effects of the activated macrophages were correlated with the amount of NO synthesis, and totally abrogated by the use of NOS inhibitor, NG-monomethyl-L-arginine (NGMMA). The increases in NO synthesis was reflected as increased amounts of iNOS mRNA by Northern blotting. To confirm that iNOS induction was due to the changes in the intracellular Ca2+ level, the acetoxymethyl ester of 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA-AM), an intracellular Ca2+ chelator, was used. Blocking the increase of cytosolic free Ca2+ significantly decreased the induction of NO synthesis. To demonstrate that intracellular Ca2+ acts as a 'priming' signal rather than a 'triggering' signal on the induction of NO synthesis by murine peritoneal macrophages, we designed several experiments. When the cells were treated with TG 6 hr after the treatment with IFN-gamma, there was no increase in NO synthesis. In addition, when the cells were treated with TG or LPS 6 hr after treatment with tBuBHQ, a synergistic increase on NO synthesis was shown only in the case of LPS. When phorbol 12-myristate 13-acetate (PMA), a protein kinase C (PKC) activator, was added to the cells 6 hr after the treatment with TG, there was a marked co-operative induction of NO synthesis, even though PMA alone has no effect. Based on the results obtained in this study, we suggest that cytosolic Ca2+ might be enough for the expression of iNOS gene as a priming signal and PKC might be involved in the induction of NO synthesis as a triggering signal by post-transcriptional modification of iNOS mRNA or iNOS itself in the activated murine peritoneal macrophages.
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PMID:Role of intracellular calcium as a priming signal for the induction of nitric oxide synthesis in murine peritoneal macrophages. 869 94


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