UNIPROT:P20020 - FACTA Search

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Query: UNIPROT:P20020 (adenosine triphosphatase)
3,299 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We previously demonstrated that vascular smooth muscle cells possess a prominent Na+-K+-Cl- cotransport system that can be markedly stimulated by elevations in levels of intracellular cyclic guanosine 3',5'-monophosphate (cGMP). Since others have shown that atrial natriuretic factor (ANF) can bind to specific membrane receptors and can enhance cGMP levels in vascular smooth muscle cells, we asked whether ANF could also stimulate Na+-K+-Cl- cotransport in vascular smooth muscle cells. It was discovered that rat atriopeptin III stimulated Na+-K+-Cl- cotransport of vascular smooth muscle cells in a concentration-dependent manner. In contrast, rat atriopeptin III had no effect on two other sodium transport systems known to be present in vascular smooth muscle cells (i.e., Na+-H+ exchange and Na+-K+-adenosine triphosphatase (ATPase). These studies indicated that ANF selectively stimulates Na+-K+-Cl- cotransport of vascular smooth muscle cells. We then asked whether ANF-stimulated Na+-K+-Cl- cotransport was dependent upon the ability of ANF to enhance intracellular cGMP levels. When rat atriopeptin III-stimulated increases in cGMP were inhibited with the quinolinedione LY 83583, rat atriopeptin III could no longer stimulate Na+-K+-Cl- cotransport of vascular smooth muscle cells. Thus it appeared that the effects of ANF were dependent upon the ability of ANF to elevate intracellular cGMP levels. Finally, we asked whether ANF effects on Na+-K+-Cl- cotransport were related to the biological activity of ANF.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of atrial natriuretic factor on Na+-K+-Cl- cotransport of vascular smooth muscle cells. 282 61

Atrial natriuretic peptides (ANPs) cause vasorelaxation, natriuresis and diuresis. Although the precise mechanism of action for these biological activities is not known, it has been established that ANPs can bind to specific membrane receptors and can cause an increase in intracellular cyclic GMP (cGMP) levels. In previously published studies we have probed the mechanism of action of ANP and have shown that one consequence of ANP receptor-mediated increases in cGMP in vascular smooth muscle cells (VSMC) is stimulation of Na/K/Cl cotransport. Although others have suggested that ANPs may affect Na/H exchange and/or Na/K adenosine triphosphatase (ATPase) activity in various cells and tissues, the effect of ANPs on these other Na transport systems in VSMC is not known. Furthermore, the biological relevance of ANP-stimulation of Na/K/Cl cotransport in VSMC has not been established. The goal of the present study was to investigate whether ANPs selectively stimulate Na/K/Cl cotransport in VSMC and to determine whether effects on cotransport parallel biological activity. We tested the effect of six ANPs on Na/K/Cl cotransport, and of one ANP on Na/H exchange and on Na/K ATPase activity. It was found that ANPs stimulated Na/K/Cl cotransport but had no effect on Na/H exchange or on Na/K ATPase activity in VSMC. Biological activity of the ANPs was assayed by measuring the potencies for producing vasorelaxation of aortic rings and for stimulating an increase in intracellular cGMP in VSMC. The rank orders observed for the two biological activities agreed with the rank order for stimulation of Na/K/Cl cotransport.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Biologically active atrial natriuretic peptides selectively activate Na/K/Cl cotransport in vascular smooth muscle cells. 282 59

Transmission electron microscopy and ultracytochemistry were employed in an attempt to localize the enzyme calcium adenosine triphosphatase (Ca-ATPase) in the rod outer segments (ROS) of the toad retina. Utilizing a one-step incubation procedure, Ca-ATPase was identified as an electron-dense precipitate in the intradiskal spaces of the rod disks (vesicles) of the ROS. Analytical microscopy identified the reaction product as lead phosphate. The formation of the reaction product was dependent on the presence of ATP (the substrate) and calcium ions. However, calcium ions could be substituted for by magnesium ions. In addition, the reaction was vanadate sensitive. The latter is known to inhibit Ca-ATPase activity. Such data appear to indicate the presence of a Ca-Mg-ATPase in association with the rod disks. Since cyclic guanosine monophosphate (cyclic GMP), rather than calcium ions, is currently believed to be the primary intracellular messenger associated with phototransduction, the presence of an ROS Ca-ATPase may indicate other functions for this cation in the physiology and biochemistry of the visual process. Ca-ATPase might play a role in directional calcium fluxes between intracellular compartments.
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PMID:Electron microscopic cytochemical localization of Ca-ATPase in the rod outer segments of the toad Bufo marinus. 297 64

A newly synthesized compound, N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA-1004), was shown to be a potent inhibitor of two cyclic nucleotide-dependent protein kinases, cyclic GMP-dependent protein kinase and cyclic AMP-dependent protein kinase and the Ki values were 1.4 and 2.3 microM, respectively. HA-1004 relaxed rabbit aortic strips contracted by various agonists and with similar ED50 values. Phenotolamine, propranolol and atropine did not affect this HA-1004-induced relaxation, thereby suggesting that this compound does not act through these membrane receptor associated mechanisms. HA-1004 shifted the dose-response curve for CaCl2 to the right in a competitive manner in depolarized rabbit renal arterial strips. This compound also relaxed the A-23187 and phenylephrine-induced contractions elicited in Ca++-free solution. These findings suggest that HA-1004 exerts its action at the intracellular or submembranal level. This vasodilator has little effect on actomyosin adenosine triphosphatase and Ca++-calmodulin-dependent myosin light chain kinase. Studies using its derivatives with various lengths of alkyl chain (C0-C6) indicated that the potencies of these compounds, as vasorelaxants, correlated well with their potential to inhibit cyclic nucleotide-dependent protein kinase. HA-1004 should be a useful tool for investigating in smooth muscle, regulatory mechanism(s) by second messengers, cyclic AMP and cyclic GMP.
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PMID:Relaxation of vascular smooth muscle by HA-1004, an inhibitor of cyclic nucleotide-dependent protein kinase. 299 36

These in vitro studies of golden hamster sperm were undertaken to determine whether: Na+, K+-adenosine triphosphatase (ATPase) activity is required for capacitation; Na+, K+-ATPase activity is altered during capacitation; and cyclic nucleotides can control this enzyme activity. Hamster sperm were incubated in a medium in which capacitation occurred in an asynchronous manner and in which acrosome reactions began to occur after approximately 3.5 h of incubation. Inhibition of the hamster sperm acrosome reaction by the Na+, K+-ATPase inhibitor ouabain (1 microM) added at Time (T) = 2 or T = 3 h could be fully reversed by the addition of the ionophore nigericin (0.1 microM) at T = 3.5 h. However, when ouabain was added at T = 0 or T = 1 h, similar nigericin addition could not completely reverse the inhibition. Na+, K+-ATPase activity of hamster sperm increased by 2 h of incubation (compared to that measured initially after 15 min) and this activity remained elevated at 3.5 h. Addition of either monobutyryl cyclic adenosine 3':5'-monophosphate ( BtcAMP ) (12.9 microM) or monobutyryl cyclic guanosine monophosphate ( BtcGMP ) (10.5 microM), or the phosphodiesterase inhibitor SQ20009 (10 microM) at 2 h produced a stimulation of acrosome reactions at 4 and 5 h. However, while BtcGMP and SQ 20009 also induced a further increase in Na+, K+-ATPase activity measured at 3.5 h, BtcAMP had no effect. Intracellular cAMP and cGMP levels measured showed cAMP increased by 2 h and remained elevated when measured at 3.5 h, while cGMP could not be consistently detected at 15 min, 2 h or 3.5 h. However, assays of high numbers of uncapacitated sperm did detect a low level of cGMP. These results suggest that Na+, K+-ATPase activity increases in and is essential for early capacitation [and thereby eventually for the acrosome reaction (AR)] of hamster sperm and that the increase in Na+, K+-ATPase activity occurring during capacitation is probably mediated by intracellular cGMP but not cAMP, although both cyclic nucleotides stimulate the hamster sperm AR.
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PMID:Hamster sperm Na+, K+-adenosine triphosphatase: increased activity during capacitation in vitro and its relationship to cyclic nucleotides. 632 71

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. This study was designed to determine the role of sodium-potassium adenosine triphosphatase (Na(+)-K(+)-ATPase) in the regulation of human corpus cavernosum smooth muscle contractility by nitric oxide (NO). In addition, we determined if the modulation of Na(+)-K(+)-ATPase activity by NO is dependent on the increase in intracellular cyclic GMP concentration. 2. The effect of NO donors, sodium-nitroprusside (SNP) and S-nitroso-glutathione (S-NO-Glu), and a permeable cyclic GMP analogue, 8-bromo-cyclic GMP, on Na(+)-K(+)-ATPase activity (measured as ouabain-sensitive 86Rb-uptake) was studied in human cultured corpus cavernosum smooth muscle cells (HCCSMC). In addition, the effect of the cyclic GMP lowering agent, methylene blue, on NO-induced increase in Na(+)-K(+)-ATPase activity was studied. 3. SNP (1 microM) caused time-dependent increases in ouabain-sensitive Rb-uptake (33-72%) over 2-20 min in HCCSMC. The stimulation of ouabain-sensitive Rb-uptake by SNP was concentration-dependent (30 and 102% with 0.1 and 1 microM SNP, respectively). Similarly, significant increases in ouabain-sensitive Rb-uptake were obtained with 1 and 10 microM S-NO-Glu. In contrast, incubation of HCCSMC with 8-bromo-cyclic GMP (100 microM) did not increase ouabain-sensitive Rb-uptake. 4. S-NO-Glu induced-increase in intracellular cyclic GMP synthesis, but not the increase in ouabain-sensitive Rb-uptake, was completely inhibited by methylene blue in HCCSMC. 5. The Na(+)-K(+)-ATPase inhibitor, ouabain, caused a concentration-dependent increase in tension (0.5 to 2 fold) in tissues contracted with 15 mM KCl. SNP and S-NO-Glu caused a concentration-dependent relaxation (concentration required to cause half maximal relaxation (ED50) = 0.04 and 0.2 microM, respectively) of HCC strips contracted with 15 mM K+. Ouabain (0.1 to 10 microM) inhibited the response to SNP and S-NO-Glu by shifting the concentration-response curves to the right and preventing full smooth muscle relaxation.6. These results indicate that the activity of Na+-K+-ATPase modulates the contractility of HCC smooth muscle, and that NO stimulates Na+-K+-ATPase activity in HCCSMC independently of its ability to increase the intracellular cyclic GMP concentration. They also suggest that stimulation of Na+-K+-ATPase activity plays an important role in NO-induced relaxation of HCC smooth muscle
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PMID:Possible role of Na(+)-K(+)-ATPase in the regulation of human corpus cavernosum smooth muscle contractility by nitric oxide. 856 49

To elucidate the effect of hypoxia on nitrovasodilator-induced pulmonary vasodilation, we studied canine pulmonary arterial rings under isometric conditions in vitro. Exposure to hypoxia inhibited the relaxant responses of KCl-contracted tissues to sodium nitroprusside (SNP), so that the maximal relaxation (Emax) and the negative logarithm of molar concentration required to produce 50% relaxation (pD2) were decreased from 92 +/- 7 to 62 +/- 5% and from 5.8 +/- 0.2 to 4.7 +/- 0.3, respectively (means +/- SE, P < 0.01 for each). This effect was likewise observed when 8-bromoguanosine-3',5'-cyclic monophosphate was used as a relaxant. The impairment of SNP-induced relaxation of endothelium-denuded rings under hypoxia was abolished by ouabain or K(+)-free solution. Incubation with SNPincreased intracellular cGMP contents in a dose dependent manner, an effect that was not altered by hypoxia. SNP also increased ouabain-sensitive 86Rb uptake, and this effect was inhibited by hypoxia. These results suggest that hypoxia reduces nitrovasodilator-induced relaxation of pulmonary artery, probably through an inhibition of cGMP-dependent sarcolemmal Na-K-adenosine triphosphatase activity.
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PMID:Hypoxia impairs nitrovasodilator-induced pulmonary vasodilation: role of Na-K-ATPase activity. 876 Jan 48

The present study was designed to investigate the role of the sodium potassium adenosine triphosphatase (the Na(+)K(+) ATPase) in relaxation of bovine isolated bronchioles by a new NO donor, GEA 3175 (3-(3-chloro-2-methylphenyl)-5-[[(4-methylphenyl)sulphonyl]amino]-)hydroxide)). Bronchioles were mounted in a wire myograph for isometric tension recordings and contracted with 5-hydroxytryptamine (5-HT) or a K(+) rich solution. Concentration-dependent relaxations evoked by GEA 3175 were inhibited by ouabain or K(+) free solution. The guanylyl cyclase inhibitor 1H-[1,2,4]-oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ, 3 microM) and ouabain (10 nM) reduced GEA 3175-evoked relaxations to the same extent without any additive effect. Iberiotoxin (10 nM), an inhibitor of large conductance Ca(2+)-activated K(+) channels inhibited GEA 3175-evoked relaxations to the same extent as ouabain. Combining ouabain and iberiotoxin completely abolished GEA 3175 relaxation. An inhibitor of protein kinase G (PKG), Rp-beta-phenyl-1,N(2)-etheno-8-bromo-guanosine-3'-5'-cyclic monophosphorothioate (Rp-8-Br-PET-cGMPs), slightly reduced GEA 3175-induced relaxations. An inhibitor of cyclic AMP-dependent kinase (PKA), Rp-adenosine-3'-5'-cyclic phosphorothioate (Rp-cAMPs), inhibited the GEA 3175-induced relaxations to the same extent as ouabain. Inhibition of both PKG and PKA abolished GEA 3175 relaxation. The study provides evidence that the NO donor GEA 3175 causes guanylyl cyclase-dependent relaxations, taking place through cyclic GMP and cyclic AMP-dependent protein kinases followed by opening of large conductance Ca(2+)-activated K(+) channels and activation of smooth muscle Na(+)K(+) ATPase.
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PMID:Involvement of guanylyl cyclase, protein kinase A and Na+ K+ ATPase in relaxations of bovine isolated bronchioles induced by GEA 3175, an NO donor. 1602 94

Dopamine (DA) and atrial natriuretic factor (ANF) share a number of physiological effects. We hypothesized that ANF and the renal dopaminergic system could interact and enhance the natriuretic and diuretic effects of the peptide. We have previously reported that the ANF-stimulated DA uptake in renal tubular cells is mediated by the natriuretic peptide type-A receptor (NPR-A). Our aim was to investigate the signaling pathways that mediate ANF effects on renal 3H-DA uptake. Methylene blue (10 microM), an unspecific inhibitor of guanylate cyclase (GC), blunted ANF elicited increase of DA uptake. ODQ (10 microM) a specific inhibitor of soluble GC, did not modify DA uptake and did not reverse ANF-induced increase of DA uptake; then the participation of nitric oxide-dependent pathways must be discarded. The second messenger was the cGMP since the analogous 125 microM 8-Br-cGMP mimicked ANF effects. The specific inhibitor of the protein kinase G (PKG), KT 5823 (1 microM) blocked ANF effects indicating that PKG is involved. We examined if ANF effects on DA uptake were able to modify Na+, K+ -adenosine triphosphatase (Na+, K+ -ATPase) activity. The experiments were designed by means of inhibition of renal DA synthesis by carbidopa and neuronal DA uptake blocked by nomifensine. In these conditions renal Na+, K+ -ATPase activity was increased, in agreement with the decrease of DA availability. When in similar conditions, exogenous DA was added to the incubation medium, the activity of the enzyme tended to decrease, following to the restored availability of DA. The addition of ANF alone had similar effects to the addition of DA on the sodium pump, but when both were added together, the activity of Na(+), K(+)-ATPase was decreased. Moreover, the extraneuronal uptake blocker, hydrocortisone, inhibited the latter effect. In conclusion, ANF stimulates extraneuronal DA uptake in external cortex tissues by activation of NPR-A receptors coupled to GC and it signals through cGMP as second messenger and PKG. Dopamine and ANF may achieve their effects through a common pathway that involves reversible deactivation of renal tubular Na+, K+ -ATPase activity. This mechanism demonstrates a DA-ANF relationship involved in the modulation of both decreased sodium reabsorption and increased natriuresis.
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PMID:Signaling pathways involved in atrial natriuretic factor and dopamine regulation of renal Na+, K+ -ATPase activity. 1700 63

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