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)

We have previously demonstrated that baroreceptor discharge sensitivity is depressed in dogs with experimental heart failure and that this depressed sensitivity can be reversed by the Na+,K(+)-ATPase inhibitor ouabain. This suggests that enhanced Na+,K(+)-ATPase activity in baroreceptors is responsible for the blunted baroreceptor discharge sensitivity seen in heart failure state. Because aldosterone, a known stimulator of Na+,K(+)-ATPase, is elevated in heart failure the present study was undertaken to determine the effects on baroreceptor discharge of perfusion of the carotid sinus with aldosterone in normotensive dogs. Single unit baroreceptor activity was recorded as well as carotid sinus pressure and the diameter of the carotid sinus. Perfusion of the carotid sinus with aldosterone (in Krebs-Henseleit solution) significantly elevated threshold pressure (108.5 +/- 3.1 mm Hg versus 92.7 +/- 4.6 mm Hg, p less than 0.05) and reduced peak discharge rate (40.3 +/- 3.9 spikes/sec, p less than 0.05). These effects appeared 15 minutes after aldosterone perfusion and remained constant for the next 60 minutes. There was no change in the carotid sinus pressure-diameter curve during perfusion with aldosterone. Perfusion of the carotid sinus with ouabain (0.1 microgram/ml) during aldosterone perfusion did not reverse the blunted baroreceptor discharge. The blunted baroreceptor activity induced by perfusion of the carotid sinus with aldosterone was prevented by removal of the endothelial cells in the carotid sinus area with a balloon-tipped catheter or by perfusion with saponin. Finally, perfusion of the carotid sinus with spironolactone (10 ng/ml), a mineralocorticoid receptor antagonist, prevented the inhibitory effect of aldosterone. These data suggest that aldosterone reduces maximum baroreceptor discharge.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Aldosterone reduces baroreceptor discharge in the dog. 154 52

To estimate the early effect of aldosterone on the number of active Na(+)-K+ pumps at the basolateral membrane of amphibian tight epithelia, we have measured the initial rate (at 4 min) of [3H]ouabain binding to the basolateral membrane of intact monolayers of A6 cells grown on permeable supports. Within 3 h, aldosterone induced a threefold increase of the Na transport and, simultaneously, a twofold increase of the binding rate of ouabain. Because the affinity of ouabain, estimated either by equilibrium binding studies or inhibition kinetics, was not modified by aldosterone, the effect on the initial rate of ouabain binding was due to an increase in the number of binding sites. This effect on ouabain binding was not prevented by 10 microM amiloride, which reduced the transepithelial sodium transport below control level. By contrast, the effect of aldosterone on ouabain binding was abolished by cycloheximide (5 micrograms/ml) or actinomycin D (2 micrograms/ml), doses which inhibited the aldosterone-dependent sodium transport response. These data suggest that aldosterone elicits an early, sodium-independent, protein synthesis-dependent increase in the expression of active Na(+)-K(+)-ATPase molecules.
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PMID:Sodium-independent effect of aldosterone on initial rate of ouabain binding in A6 cells. 156 17

Atrial natriuretic factor is the main natriuretic hormone. It is a peptide secreted by the atria in response to an increase of the central blood volume. Its effects are opposed to those of the renin angiotensin system and all result in the decrease of volemia. The main of them are an increase in renal sodium excretion, decrease in vascular resistance, increase in capillary permeability, and inhibition of renin and aldosterone secretions. ANF stimulates, via its B receptors, the production of cyclic GMP which is its second messenger. ANF is catabolized by clearance receptors which internalize it and ectoenzymes, mainly neutral endoproteinase. Plasma ANF increases in various conditions for three essential reasons: increase of its secretion from the usual sources, increase of its secretion from supplementary sites, decrease of its catabolism. Since ANF is implied in the maintenance of homeostasis in several diseases, treatment by neutral endoproteinase inhibitors which increases plasma ANF has been considered. Another natriuretic factor structurally close to digitalin and inhibiting Na(+)-K+ ATPase has been described but not identified.
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PMID:[Natriuretic factors]. 160 57

Exposure of Clone 9 cells, a "nontransformed" rat liver cell line, to 10(-8) M dexamethasone resulted at 3 h in 1.8 +/- 0.2- and 40 +/- 5-fold increases in mRNA alpha 1 and mRNA beta 1 content, respectively, an effect that was not mimicked by 10(-8) M aldosterone. The increments in mRNA alpha 1 and mRNA beta 1 abundances in total cell RNA were half-maximal at 5 x 10(-9) M dexamethasone and persisted for more than 24 h. Na,K-ATPase activity, however, increased only slightly (by 9%) at 24 h. The induction of mRNA beta 1 by dexamethasone was not prevented by the presence of cycloheximide. mRNA beta 1 abundance increased earlier in the nuclear RNA pool (becoming apparent within 45 min) than in the cytoplasmic RNA pool, consistent with a precursor-product relationship. Moreover, putative pre-mRNA beta 1 bands of approximately 4,600 and approximately 12,000 nucleotides accumulated in the nRNA pool after 1 h of exposure to dexamethasone. Incubation in the presence of dexamethasone for 3 h enhanced the incorporation of [3H]uridine into total cell mRNA alpha 1 and mRNA beta 1 by 1.3- and 12-fold, respectively. In nuclear run-on assays, however, transcription of mRNA alpha 1 and mRNA beta 1 was not altered after 30 min of exposure to 10(-8) M dexamethasone. The abundance of mRNA beta 1 in rat liver also increased markedly (greater than 30-fold) in rats treated with the hormone for 6 h. We conclude that dexamethasone causes an induction of Na,K-ATPase subunit mRNAs, an effect that is markedly greater for mRNA beta 1 than for mRNA alpha 1. The increases in subunit mRNA content, however, are associated with, at most, a small increase in Na,K-ATPase activity, suggesting that the increments in mRNA abundances, especially that of mRNA beta 1, do not play a determining role in the regulation of Na,K-ATPase activity in these cells.
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PMID:Dexamethasone markedly induces Na,K-ATPase mRNA beta 1 in a rat liver cell line. 164 12

By altering the Na+/K+ electrochemical gradient, Na+,K(+)-ATPase activity profoundly influences cardiac cell excitability and contractility. The recent finding of mineralocorticoid hormone receptors in the heart implies that Na+,K(+)-ATPase gene expression, and hence cardiac function, is regulated by aldosterone, a corticosteroid hormone associated with certain forms of hypertension and classically involved in regulating Na+,K(+)-ATPase gene expression and transepithelial Na+ transport in tissues such as the kidney. The regulation by aldosterone of the major cardiac Na+,K(+)-ATPase isoform genes, alpha-1 and beta-1, were studied in adult and neonatal rat ventricular cardiocytes grown in defined serum-free media. In both cell types, aldosterone-induced a rapid and sustained 3-fold induction in alpha-1 mRNA accumulation within 6 h. beta-1 mRNA was similarly induced. alpha-1 mRNA induction occurred over the physiological range with an EC50 of 1-2 nM, consistent with binding of aldosterone to the high affinity mineralocorticoid hormone receptor. In adult cardiocytes, this was associated with a 36% increase in alpha subunit protein accumulation and an increase in Na(+)-K(+)-ATPase transport activity. Aldosterone did not alter the 3-h half-life of alpha-1 mRNA, indicating an induction of alpha-1 mRNA synthesis. Aldosterone-dependent alpha-1 mRNA accumulation was not blocked by the protein synthesis inhibitor cycloheximide, whereas amiloride inhibited both an aldosterone-dependent increase in intracellular Na+ [Na+]i) and alpha-1 mRNA accumulation. This demonstrates that aldosterone directly stimulates Na+,K(+)-ATPase alpha-1 subunit mRNA synthesis and protein accumulation in cardiac cells throughout development and suggests that the heart is a mineralocorticoid-responsive organ. An early increase in [Na+]i may be a proximal event in the mediation of the hormone effect.
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PMID:Aldosterone-mediated regulation of Na+, K(+)-ATPase gene expression in adult and neonatal rat cardiocytes. 164 19

The recently synthesized progesterone (P) derivatives, 18-vinylprogesterone (18VP) and 18-ethynylprogesterone (18EP), are potent inhibitors of aldosterone synthesis by adrenal glands. To evaluate the potential interest of these compounds as antihypertensive drugs, we determined whether they also interact with renal mineralocorticosteroid receptors (MR) in kidney and, if so, whether they mimic or antagonize aldosterone action. For this purpose, we evaluated the potency of 18VP and 18EP 1) to displace [3H]aldosterone binding in cytosolic fractions of kidney from adrenalectomized rats and 2) to interfere with aldosterone-induced stimulation of Na(+)-K(+)-ATPase in the collecting tubule of adrenalectomized rats. The properties of 18VP and 18EP were compared with those of their precursor progesterone and of the antimineralocorticosteroid spironolactone. The binding of [3H]aldosterone was restricted to cytosolic MR by presaturating glucocorticosteroid receptor with RU 38486. All compounds tested displaced [3H]aldosterone binding with the following efficiency: spironolactone greater than aldosterone greater than P greater than 18VP greater than 18EP; apparent Kd varied between 0.66 and 16.4 nM. Spironolactone, P, and 18VP antagonized aldosterone-induced stimulation of Na(+)-K(+)-ATPase in the collecting tubule, whereas 18EP mimicked the mineralocorticosteroid action. The different steroids tested altered Na(+)-K(+)-ATPase stimulation and aldosterone binding with the same order of potency.
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PMID:Renal action of progesterone and 18-substituted derivatives. 164 87

1. In the nephrotic syndrome the kidneys retain salt and water, which leads to oedema formation. The site of this sodium retention has been localized in the cortical collecting tubule by micropuncture studies. Whether or not this phenomenon is an intrinsic renal problem or is the consequence of changes in hormonal activities is still a matter of discussion. 2. Using the model of puromycin aminonucleoside-induced nephrotic syndrome in the rat, we measured Na+,K(+)-ATPase activity in nephron segments from control and nephrotic rats and investigated the regulatory role of aldosterone and endogenous-ouabain-displacing factor. 3. Nephrotic animals had a twofold increase in Na+,K(+)-ATPase activity in the cortical collecting tubule only (control versus nephrotic: 1065 +/- 68 versus 2081 +/- 274 pmol h-1 mm-1, P = 0.036), which was not modified by adrenalectomy and was independent of the kidney content of endogenous ouabain-displacing factor. Na+,K(+)-ATPase activity in the cortical collecting tubule correlated with the sodium balance in both control and nephrotic rats. 4. The data are consistent with the view that sodium retention in this model of the nephrotic syndrome is a primary event, i.e. an increase in sodium transport throughout the cortical collecting tubule expressed as a twofold increase in Na+,K(+)-ATPase activity which is no longer under hormonal regulation (aldosterone and endogenous ouabain-displacing factor).
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PMID:Na+,K(+)-ATPase activity and hormones in single nephron segments from nephrotic rats. 164 23

Isolated rat hepatocytes possess a saturable glucocorticoid uptake system with high affinity (Kd value = 2.8 +/- 0.7 x 10(-8) M; 318,000 +/- 80,000 binding sites per cell; 317 fmol/mg protein). The initial rates of uptake decrease by about 30-40% if the cells are incubated simultaneously with [3H]corticosterone and either SH-reagents (N-ethylmaleimide and p-chloromercuriphenylsulphonate, 1 mM), metabolic inhibitors (2,4-dinitrophenol, 1 mM; and antimycin, 0.1 mM) or the Na+/K(+)-ATPase-inhibitors, ouabain and quercetine. These Na+/K(+)-ATPase-blockers exert half-maximal inhibition at 3 x 10(-7) and 3 x 10(-6) M, respectively. A slight increase in K+ concentration and a corresponding decrease in Na+ in the medium leads to a significant reduction in the initial uptake rate. The uptake system from the rat hepatocytes shows a clear steroid specificity, being different from the intracellular receptor. Corticosterone and progesterone are the strongest competitors, cortisol, 5 alpha- and 5 beta-dihydrocorticosterone, 11-deoxycorticosterone, cortisone and testosterone have an intermediate effect and only weak competition is exerted by dexamethasone and by the mineralocorticoid, aldosterone. Estradiol and estrone sulphate as well as the synthetic glucocorticoid triamcinolone acetonide are unable to inhibit initial corticosterone uptake.
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PMID:Uptake of corticosterone into isolated rat liver cells: possible involvement of Na+/K(+)-ATPase. 164 77

To evaluate the importance of an endogenous sodium pump inhibitor in the pathogenesis of low renin human hypertension, the urinary excretion of a digoxin-like immunoreactive substance (DLIS) was measured in eight patients with primary aldosteronism (n = 5, with adenomas) during two sequential 1-week periods of low- (20 mmol/l NaCl) and high- (200 mmol/l NaCl) sodium intake. DLIS excretion increased consistently during high-sodium intake while urinary aldosterone, plasma renin activity, cortisol and adrenocorticotropic hormone did not change. Although blood pressure showed a time-course parallel to that of the urinary DLIS, the blood pressure increments were not accompanied by evidence of vasoconstriction since forearm blood flow (plethysmographic technique) increased and forearm vascular resistances were reduced. Moreover, the reactivity of forearm arterioles to local norepinephrine was unchanged during the period of low- and high-salt intake, despite the fact that an endogenous sodium pump inhibitor should, supposedly, sensitize the responses to an adrenergic agonist. Finally, forearm vasoconstrictor responses to ouabain, a pharmacological Na+,K(+)-ATPase antagonist, were potentiated during the high-salt diet, a result not expected if an increased number of sodium pumps were occupied by an endogenous inhibitor. These results provide unequivocal evidence for a modulation by salt intake of the urinary excretion of a DLIS in patients with primary aldosteronism. This substance might participate in the regulation of body fluid volume in this syndrome and possibly in other physiological conditions. However, no evidence could be found for a cause--effect relationship between blood pressure and DLIS increments during high-salt intake, at least during the short-term course of the study.
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PMID:Does a digoxin-like substance participate in vascular and pressure control during dietary sodium changes in patients with primary aldosteronism? 164 66

Fast and slow K+ efflux components, independently regulated by angiotensin II (AII), have been identified in bovine adrenocortical cells. We have further investigated the role of potassium in the control of aldosterone synthesis in two ways. Firstly, isotopic tracers, in conjunction with channel modulators, have been used to study the interrelationship of K+ and Ca2+ in the control of AII-stimulated aldosterone synthesis. Secondly, electron probe X-ray microanalysis (EPXMA) was used to quantify potassium, sodium, chlorine and phosphorous in control and AII-stimulated cells. The effects of verapamil on 43K efflux were measured at two stages during AII stimulation. During the first ten minutes of treatment, when efflux via the fast component predominates, AII and verapamil both slowed efflux and their effects were additive. If verapamil was added later, at the time when efflux by the fast component appeared exhausted and the stimulatory effect of AII on the slow efflux component was apparent, it again slowed efflux. These data suggest that verapamil prevents calcium-gated K+ channels from opening by blocking Ca2+ channels. However, verapamil had no effect on AII-stimulated calcium efflux. In addition to blocking Ca2+ channels, verapamil may directly inhibit potassium efflux. EPXMA showed a bimodal distribution of potassium concentrations in control cells. However, in cells stimulated with AII for five minutes, the mean potassium content was less than in controls and was not bimodally distributed. Sodium content was increased by AII-treatment, chlorine was lowered and phosphorus remained unchanged. The data confirm previous observations that AII inhibits Na+/K+ ATPase activity.
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PMID:The role of potassium and other ions in the control of aldosterone synthesis. 165 31


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