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)

We examined whether Ca(2+) mobilizers induce endothelium-dependent contraction and relaxation (EDC and EDR) in isolated rabbit intrapulmonary arteries. Ionomycin (10(-7) M) and A-23187 (10(-7) M), both Ca(2+) ionophores, and thapsigargin (10(-6) M), an endoplasmic reticulum Ca(2+)-ATPase inhibitor, caused a contraction in the non-contracted preparations, and a transient relaxation followed by a transient contraction and sustained relaxation in the precontracted preparations. Endothelium-removal abolished the contraction and transient relaxation (EDC and EDR) but not sustained relaxation (endothelium-independent relaxation, EIR). In the noncontracted preparations, ionomycin-induced EDC was significantly attenuated by quinacrine (10(-5) M), manoalide (10(-6) M), both phospholipase A(2) inhibitors, indomethacin (10(-5) M) and aspirin (10(-4) M), both COX inhibitors, and ozagrel (10(-5) M), a TXA(2) synthetase inhibitor. In the precontracted arteries, EDR was markedly reduced by L-NAME (10(-4) M), a NOS inhibitor, and methylene blue (10(-6) M), a guanylate cyclase inhibitor, and was enhanced by indomethacin, aspirin and ozagrel, probably due to inhibition of EDC. ZM230487, a 5-lipoxygenase inhibitor, had no effect on EDR. EIR was not affected by L-NAME, indomethacin or ZM230487. Arachidonic acid (10(-6) M) evoked EDC sensitive to indomethacin and ozagrel. L-Arginine (10(-3) M) caused EDR sensitive to L-NAME in the ionomycin-stimulated preparations. In conclusion, Ca(2+) mobilizers cause EDC and EDR via production of TXA(2) and NO, respectively.
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PMID:Role of intracellular Ca2+ in endothelium-dependent contraction and relaxation of rabbit intrapulmonary arteries. 1258 21

The aim of this study was to investigate the effect of nitric oxide on renal Na+,K(+)-ATPase and ouabain-sensitive H+,K(+)-ATPase activities. The study was performed in male Wistar rats. The investigated substances were infused under general anaesthesia into abdominal aorta proximally to the renal arteries. The activity of ATPases was assayed in isolated microsomal fraction. NO donor, S-nitroso-N-acetylpenicillamine (SNAP), infused at doses of 10(-7) and 10(-6)mol/kg/min decreased medullary Na+,K(+)-ATPase activity by 29.4% and 45.2%, respectively. Another NO donor, spermine NONOate, administered at the same doses reduced Na+,K(+)-ATPase activity in the renal medulla by 31.7% and 46.5%, respectively. Neither of NO releasers had any effect on Na+,K(+)-ATPase in the renal cortex and on either cortical or medullary ouabain-sensitive H+,K(+)-ATPase. Infusion of NO precursor, L-arginine (100 micromol/kg/min), decreased medullary Na+,K(+)-ATPase activity by 32.2%, whereas inhibitor of nitric oxide synthase, L-NAME (10 nmol/kg/min), increased this activity by 20.7%. The effect of synthetic NO donors was mimicked by 8-bromo-cGMP and blocked by inhibitors of soluble guanylate cyclase, ODQ or methylene blue, as well as by specific inhibitor of protein kinase G, KT5823. In addition, inhibitory effect of either SNAP or 8-bromo-cGMP on medullary Na+,K(+)-ATPase was abolished by 17-octadecynoic acid (17-ODYA), which inhibits cytochrome P450-dependent metabolism of arachidonic acid. These data suggest that NO decreases Na+,K(+)-ATPase activity in the renal medulla through the mechanism involving cGMP, protein kinase G, and cytochrome P450-dependent arachidonate metabolites. In contrast, NO has no effect on Na+,K(+)-ATPase in the renal cortex and on either cortical or medullary ouabain-sensitive H+,K(+)-ATPase.
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PMID:Nitric oxide decreases renal medullary Na+, K+-ATPase activity through cyclic GMP-protein kinase G dependent mechanism. 1283 21

It is commonly known that consumption of foods and beverages rich in polyphenols is associated with a lower incidence of cardiovascular disease. The purpose of this study was to assess whether the application of red wine polyphenols influences the kinetic properties of renal Na(+),K(+)-ATPase in rats in which hypertension has been experimentally induced by the nitric oxide synthase inhibitor L-NAME. Treatment with polyphenols during the recovery from hypertension to normotension resulted in the complete revival of the functional properties of the Na(+),K(+)-ATPase, as indicated by the total restoration of K(m), K(Na) (concentration of Na(+) necessary to achieve half-maximal reaction velocity) and V(max) for enzyme activation by ATP and/or Na(+) to pre-hypertension values. Two positive effects of polyphenols during the recovery period are indicated: a restoration of the affinity of the ATP and Na(+) binding sites to control values and a probable increase in the number of Na(+),K(+)-ATPase molecules to a level comparable to that in control conditions, as suggested by the complete renewal of V(max).
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PMID:Effect of polyphenolic compounds on the renal Na(+),K(+)-ATPase during the restoration of normotension after experimentally induced hypertension in rats. 1286 34

In the present study, we investigated the effect of Vitamins E and C on the inhibition of Na(+),K(+)-ATPase activity provoked by proline (Pro) administration in rat hippocampus. Five-day-old rats were pretreated for 1 week with daily i.p. administration of saline (control) or Vitamin E (40 mg/kg) and Vitamin C (100 mg/kg). Twelve hours after the last injection, animals received one single injection of Pro (12.8 micromol/g of body weight) or saline and were killed 1h later. Results showed that Na(+),K(+)-ATPase activity was decreased in the Pro-treated rats and that the pretreatment with Vitamins E and C prevented this effect. In another set of experiments, we investigated the in vitro effect of 1.0 mM Pro on Na(+),K(+)-ATPase activity from synaptic membranes of hippocampus of rats. Pro significantly inhibited (30%) Na(+),K(+)-ATPase activity. We also evaluated the effect of preincubating glutathione, trolox and N(pi)-nitro-L-arginine methyl ester (L-NAME) alone or combined with Pro on Na(+),K(+)-ATPase activity. Tested drugs did not alter Na(+),K(+)-ATPase activity, but glutathione prevented the inhibitory effect of Pro on this enzyme activity. These results suggest that the in vivo and in vitro inhibitory effect of Pro on Na(+),K(+)-ATPase activity is probably mediated by free radicals that may be involved in the neurological dysfunction found in hyperprolinemic patients.
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PMID:Evidence that oxidative stress is involved in the inhibitory effect of proline on Na(+),K(+)-ATPase activity in synaptic plasma membrane of rat hippocampus. 1292 78

Microelectrode and patch-clamp techniques were used in the isolated cortical collecting duct to study the effects of stimulating Na+-K+-ATPase by raising bath K+ (Fujii Y and Katz AI. Am J Physiol Renal Fluid Electrolyte Physiol 257: F595-F601, 1989 and Muto S, Asano Y, Seldin D, and Giebisch. Am J Physiol Renal Physiol 276: F143-F158, 1999) on the transepithelial (VT) and basolateral membrane (VB) voltages and basolateral K+ channel activity. Increasing bath K+ from 2.5 to 8.5 mM resulted in an initial hyperpolarization of both VT and VB followed by a delayed depolarization. The effects of raising bath K+ on VT and VB were attenuated by decreasing luminal Na+ from 146.8 to 14.0 mM and were abolished by removal of luminal Na+, whereas those were magnified in desoxycorticosterone acetate (DOCA)-treated rabbits. Increasing bath K+ also led to a significant reduction of the intracellular Na+ and Ca2+ concentrations. The transepithelial conductance (GT) or fractional apical membrane resistance (fRA) were unaltered during the initial hyperpolarization phase, whereas, in the late depolarization phase, there were an increase in GT and a decrease in fRA, both of which were attenuated in the presence of low luminal Na+ (14.0 mM). In tubules from DOCA-treated animals, bath Ba2+ not only caused a significantly larger initial hyperpolarization of VT and VB but also blunted the late depolarization by high bath K+. Nomega-nitro-l-arginine methyl ester (l-NAME) partially mimicked the effect of Ba2+ and decreased the amplitude of the late depolarization. Patch-clamp experiments showed that raising bath K+ from 2.5 to 8.5 mM resulted in an increased activity of the basolateral K+ channel, which was absent in the presence of l-NAME. We conclude that stimulation of Na+-K+-ATPase increases the basolateral K+ conductance and that this effect involves suppression of nitric oxide-dependent inhibition of K+ channels.
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PMID:Activity of the basolateral K+ channels is coupled to the Na+-K+-ATPase in the cortical collecting duct. 1453 63

The present study investigated sodium balance and renal tubular function in cirrhotic rats with chronic blockade of the nitric oxide (NO) system. Rats were treated with the nonselective NO synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME) starting on the day of common bile duct ligation (CBL). Three weeks of daily sodium balance studies showed that CBL rats developed sodium retention compared with sham-operated rats and that l-NAME treatment dose dependently deteriorated cumulative sodium balance by reducing urinary sodium excretion. Five weeks after CBL, renal clearance studies were performed, followed by Western blotting of the electroneutral type 3 sodium/proton exchanger (NHE3) and the Na-K-ATPase present in proximal tubules. Untreated CBL rats showed a decreased proximal reabsorption with a concomitant reduction of NHE3 and Na-K-ATPase levels, indicating that tubular segments distal to the proximal tubules were responsible for the increased sodium reabsorption. l-NAME-treated CBL rats showed an increased proximal reabsorption measured by the lithium clearance method and showed a marked increase in NHE3 and Na-K-ATPase protein levels. Our results show that chronic l-NAME treatment exacerbates the sodium retention found in CBL rats by a significant increase in proximal tubular reabsorption.
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PMID:Chronic nitric oxide synthase inhibition exacerbates renal dysfunction in cirrhotic rats. 1458 32

L-NAME (LN) induces hypertension by blocking nitric oxide (NO) synthesis. It produces vascular hyperreactivity to phenylephrine (PHE) associated with a reduced vascular Na+, K+-ATPase activity. The aim of this work was to investigate whether products of the cyclooxygenase pathway are involved in alterations of vascular reactivity and Na+-pump activity in the tail artery from LN-induced hypertension rats. Four groups of rats were used: Control (CT, normotensive), LN (50 mg/kg/day, hypertensive), indomethacin (Indo-4 mg/kg/day, normotensive), and LN plus Indo (LN + Indo, partially prevented hypertension). All drugs were administered in drinking water during 7 days. In isolated rat tail vascular beds; the reactivity to PHE, acetylcholine (ACh), sodium nitroprusside (SNP), the functional activity of the Na+, K+-ATPase (K+-induced relaxation) and the modulation of PHE-induced vasoconstriction by constitutively available NO were evaluated. LN increased vascular sensitivity (pD2) and reactivity (Emax) to PHE and Indo blocked the effect of LN on Emax without changing pD2. Emax and pD2 values for ACh were reduced by LN and partially reverted by Indo. SNP-induced vasodilatation was similar in all groups. LN reduced the activity of Na+, K+-ATPase and Indo prevented LN effects. LN also abolished NO ability to modulate PHE-induced contractions. This effect was partially prevented by Indo suggesting that products from the cyclooxygenase pathway might reduce NO actions. Indo itself did not affect vascular reactivity to PHE, ACh or SNP or the Na+,K+-ATPase activity. Results suggested that products from cyclooxygenase pathway are involved in the genesis or maintenance of LN-induced hypertension, playing a role in the increased vascular reactivity, in the reduction of the endothelium-dependent relaxation and in the inhibition of the functional activity of the Na+, K+-ATPase.
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PMID:Cyclooxygenase pathway is involved in the vascular reactivity and inhibition of the Na+, K+-ATPase activity in the tail artery from L-NAME-treated rats. 1462 32

It has been suggested that polyphenolic substances provide protection against the risk factors of cardiovascular diseases. The present study was designed to investigate whether application of red wine polyphenols influences the kinetic properties of the renal Na+,K(+)-ATPase in rats with hypertension (164 +/- 8 mmHg) that was experimentally induced by the NO synthase inhibitor N(G.) -nitro-L- arginine methyl ester (L-NAME). Polyphenols in a dose of 40 mg kg(-1) day(-1) in drinking fluid induced different effects on the properties of the renal Na+,K(+)-ATPase depending on the mode of their administration. Preventive application of polyphenols during the development of hypertension (144 +/- 5 mmHg) partially protected the Na+,K(+)-ATPase molecule against hypertension-induced deterioration via increased capability of the enzyme to bind ATP and/or Na+ as suggested by decrease of Km and KNa, respectively, even to values lower than in controls. However, polyphenols did not prevent the hypertension-induced reduction of the number of active Na+,K(+)-ATPase molecules as shown by similar V(max) values as compared to the hypertensive L-NAME group. The above protection is probably secured by a NO-dependent mechanism as suggested by 150% increase of the NO synthesis. Additional treatment of already hypertensive animals with polyphenols (153 +/- 8 mmHg) resulted in partial restoration of the Na+,K(+)-ATPase affinities especially for sodium as indicated by significant diminution of KNa. However, polyphenols in this mode of application did not slow down the L-NAME-induced decrease in the number of Na+,K(+)-ATPase molecules in the kidney as suggested by additional significant decrease in V(max) values when comparing this group with the control group and also the hypertensive L-NAME group. In this case the polyphenols affected the Na,K-ATPase molecule in a NO-independent way as indicated by the fact that polyphenols failed to restore normal NO synthesis.
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PMID:Effect of polyphenolic compounds on the renal Na+,K(+)-ATPase during development and persistence of hypertension in rats. 1510 12

Guanidinoacetate methyltransferase deficiency (GAMT-deficiency) is an inherited neurometabolic disorder clinically characterized by epilepsy and mental retardation and biochemically by accumulation of guanidinoacetate (GAA) and depletion of creatine. Although the neurological symptoms are predominant, the pathogenesis of the brain dysfunction in this disorder is not yet established. In the present study we investigated the in vitro effect of GAA on Na+, K+-ATPase and Mg2+-ATPase activities in synaptic plasma membrane from hippocampus of young rats. Results showed that GAA significantly inhibited Na+, K+-ATPase activity without affecting Mg2+-ATPase activity. We also evaluated the effect of glutathione (GSH), trolox, Nomega-nitro-L-arginine methyl ester (L-NAME) and taurine (Tau) on the inhibition elicited by GAA on Na+, K+-ATPase activity. GSH, trolox, L-NAME and Tau per se did not alter Na+, K+-ATPase activity. However, L-NAME and taurine prevented the inhibitory effect of GAA on this enzyme activity. Our findings suggest that the inhibition of Na+, K+-ATPase activity caused by GAA is possibly mediated by nitric oxide (NO) formation and/or synaptic membrane alteration. The present data may contribute to the understanding of the neurological dysfunction characteristic of GAMT-deficient patients.
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PMID:Evaluation of the mechanism underlying the inhibitory effect of guanidinoacetate on brain Na+, K+-ATPase activity. 1524 54

Excessive excitatory action of glutamate and nitric oxide (NO) has been implicated in degeneration of striatal neurons. Evidence had been provided that Na+K+-ATPase might be involved in this process. Here we investigated whether glutamate-regulated messengers, such as NO and cyclic GMP, could modulate the activity of membrane Na+K+-ATPase. Our results demonstrated that NO donors sodium nitroprusside (SNP at 30 and 300 microM) and S-nitroso-N-acetylpenicillamine (SNAP at 200 microM) increased alpha2,3Na+K+-ATPase activity which was blocked by the NO chelator, haemoglobin and was independent of [Na+]. This regulation was associated with cGMP synthesis and mimicked by glutamate (300 microM) and 8-Br-cyclic GMP (4 mM). 8-Br-cGMP-induced stimulation of Na+K+-ATPase activity could be blocked by KT5823 (an inhibitor of cGMP-dependent protein kinase, PKG), but not by KT5720 (an inhibitor of cAMP-dependent protein kinase, PKA). N-Methyl-D-aspartate (NMDA) receptors appeared to be involved in the effect of glutamate, since MK-801 (NMDA receptor antagonist) produced a partial reduction in glutamate-induced activation of the enzyme. MK-801 was not synergistic to L-NAME (NOS inhibitor), suggesting that glutamate stimulates the NMDA-NOS pathway to activate alpha2,3 Na+K+-ATPase in rat striatum. This regulation was associated with cyclic GMP (but not cyclic AMP) synthesis. These data indicate the existence, in vitro, of a regulatory pathway by which glutamate, acting through NO and cGMP, can cause alterations in striatal alpha2,3 Na+K+-ATPase activity.
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PMID:Glutamate modulates sodium-potassium-ATPase through cyclic GMP and cyclic GMP-dependent protein kinase in rat striatum. 1562 18


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