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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The effects of low concentrations of ouabain on 22Na efflux, 86Rb influx, 45Ca uptake and cyclic AMP levels were studied in snail ganglia. Ouabain, at concentrations below that which inhibits the Na-K pump as monitored by 86Rb influx, activated "reverse mode" Na/Ca exchange, as indicated by an increased 22Na efflux and 45Ca influx. 2. With electrophysiologic recordings ouabain, in the presence of K(+)-free saline to block Na/K transport, caused a membrane hyperpolarization. These concentrations of ouabain also caused elevation of intracellular cyclic AMP levels. 3. We suggest that the ouabain-induced stimulation of Na efflux is due to a stimulation of reverse Na/Ca exchange. since Na/Ca exchange is electrogenic, these observations are most consistent with ouabain stimulation of Na/Ca exchange in a reversed direction (intracellular Na for extracellular Ca). 4. The effect on Na/Ca exchange may be secondary to a rise in intracellular cyclic AMP.
Cell Mol Neurobiol 1996 Aug
PMID:Low concentrations of ouabain stimulate Na/Ca exchange in neurons. 887 51

Cardiac enlargement due to gradual pressure overload was induced by abdominal aortic constriction in 2-day-old rats. On day 90, the functional performance of the left ventricle was assessed by acute load test (ligation of ascending aorta) in open-chest anaesthetized animals. Two subgroups, designated compensated and decompensated hypertrophy (CH and DH), were distinguished on the basis of the functional reserve of left ventricle, which was significantly impaired in DH but not in CH, and of right ventricle weight, which was markedly increased in DH but not significantly modified in CH. In total particulate fractions prepared from hypertrophied left ventricles, the levels (per g tissue) of sarcoplasmic reticulum Ca(2+)-transport systems were decreased, either slightly (by 13-16%: [3H]ryanodine binding) or moderately (by 28%: thapsigargin-sensitive Ca(2+)-ATPase activity). The number of sarcolemmal L-type Ca2+ channels ([3H]PN200-110 binding) was not modified significantly, while that of beta 1-adrenoceptors ([3H]CGP-12177 binding) was reduced, especially in the DH group (by 39%). Na+,K(+)-ATPase activity was reduced by 28% in CH and 41% in DH. [3H]Ouabain binding experiments (saturation and dissociation) indicated the existence of two high-affinity binding sites, attributable to the Na+, K(+)-ATPase alpha 3 and alpha 2 subunit isoforms; while the relatively minor alpha 3 component did not change significantly in hypertrophied ventricles, the alpha 2 component was markedly down-regulated, decreasing by 57% in CH and 82% in DH.
Mol Cell Biochem
PMID:Calcium channels and cation transport ATPases in cardiac hypertrophy induced by aortic constriction in newborn rats. 897 36

Airway epithelial cells cultured at the air-liquid interface possess highly differentiated functions and structures compared with the cells cultured under immersion. We examined the oxidative metabolism and glycolysis in cow tracheal epithelial cells on Days 3, 6, 10, and 13, cultured under three different conditions: (1) immersion culture on porous filters with apical and basolateral feeding (IM), (2) air-exposed culture on porous filters with basolateral feeding, i.e., air-liquid interface culture (AI), and (3) conventional immersion culture in plastic dishes with apical feeding (DI). Lactate production was less in AI than in IM and DI on Day 3 through Day 13, whereas cellular adenosine triphosphate content and basal O2 consumption were greater. Ouabain-sensitive and ouabain-insensitive O2 consumption, and the uncoupled O2 consumption were also greater in AI. Cytosolic lactate dehydrogenase activities on Day 10 were lower in AI, whereas alpha-ketoglutarate dehydrogenase activities were higher. The increased oxidative metabolism in AI was more pronounced at the late phase of culture (Days 10 and 13). In contrast, glycolysis remained elevated during the experiment in IM and DI. These data suggest that (I) AI begins to promote oxidative metabolism from growth phase by the provision of adequate oxygenation, and then further shifts to oxidative metabolism with differentiation; and (2) apical feeding may be responsible for the disturbance of the development of the oxidative metabolism.
Am J Respir Cell Mol Biol 1997 Jan
PMID:Increased oxidative metabolism in cow tracheal epithelial cells cultured at air-liquid interface. 899 80

Ouabain or a closely related isomer, and 'ouabain-like compound' (OLC), has been identified in plasma, by Hamlyn et al., using several physico-chemical and biological methods. Using a radioimmunoassay, the same authors later characterized an identical compound in adrenal cortex tissue and culture medium from adrenocortical cells. Nevertheless, other groups, using different immunosera, were not able to detect OLC in adrenal cortex and adrenocortical cells medium. In this report, we confirm the presence of OLC in bovine adrenal cortex and in fasciculata cells culture medium. The compound that we obtained has the same chromatographic properties as ouabain on HPLC using two types of elution systems. It presents the same mass spectrum and is able to bind to erythrocytes membranes Na(+)-K(+)-ATPase. In primary cultures of adrenocortical cells, its biosynthesis is increased after addition of pregnenolone or progesterone suggesting that these compounds may represent intermediate substrates in the biosynthetic pathway. Rhamnose readily enters the adrenocortical cell and increases slightly the biosynthesis of OLC. The present studies confirm that bovine adrenocortical cells in primary culture release an OLC with no differences with authentic ouabain using, HPLC, mass spectrometry and radioreceptor assay and suggest that OLC may be a product related to the adrenocortical steroidogenic pathway.
Mol Cell Endocrinol 1997 Jan 03
PMID:Bovine adrenocortical cells in culture synthesize an ouabain-like compound. 902 58

We investigated the influence of ion compositions on the membrane potential in LA-N-1 human neuroblastoma cells using bisoxonol as a potential-sensitive fluorescent dye. The ability of K+, ouabain, veratridine, and maitotoxin to induce membrane depolarization was evaluated. Increasing concentrations of K+ ions from 10 to 50 mM caused a dose-dependent increase of bisoxonol fluorescence, which was completely independent on Na+ and Ca2+. Ouabain (5 mM), an inhibitor of the Na+, K(+)-ATPase, failed to induce membrane depolarization. Veratridine (40 and 100 microM), a Na+ channel activator, only in the presence of 10 micrograms of Leiurus scorpion venom reduced the membrane potential. Maitotoxin (MTX) from 3 to 10 ng/mL depolarized LA-N-1 cells in a dose-dependent manner, and produced a rapid and sustained increase of intracellular free calcium monitored by means of fluorescent probe fura-2. The MTX-induced depolarization and the increase in cytosolic free calcium concentration were dependent on extracellular Ca2+ ions. On the other hand, Na+ ions also seem to be, although only partially, implicated in the MTX effects, since both the blockade of tetrodotoxin (TTX)-sensitive voltage-operated Na+ channels and the removal of Na+ ions were able to reduce the depolarization. In conclusion, our data indicate that the depolarizing action of MTX on LA-N-1 cells is Ca(2+)- and Na(+)-dependent, although the latter only partially, and that this effect is dependent on Ca2+ influx into the cells likely through a voltage-insensitive calcium-entry system.
Mol Chem Neuropathol 1997 Apr
PMID:Membrane depolarization in LA-N-1 cells. The effect of maitotoxin is Ca(2+)- and Na(+)-dependent. 916 86

The aim of the present study was to identify the mechanism(s) responsible for the alpha 1-adrenoceptor stimulated increase in potassium uptake in ventricular cardiomyocytes isolated from adult rat heart. The Na+/K+ATPase blocker ouabain the Na+/K+/2Cl(-)-cotransporter blocker bumetanide, the Na+/H(+)-exchanger blocker HOE 694 and the potassium channel blocker 4-aminopyridine were used as experimental tools. 86Rb+ was used as potassium analogue. The basal 86Rb(+)-uptake rate was 0.25 +/- 0.01 ml/g protein x min. Maximal alpha 1-adrenoceptor stimulation increased the 86Rb(+)-uptake 38 +/- 2%. Ouabain dose dependently eliminated the alpha 1-adrenoceptor stimulated response with a -logIC50-value of 3.64 +/- 0.23. Bumetanide did not affect the stimulated response, and there was no effect of bumetanide on the ouabain sensitive component. HOE 694 and 4-aminopyridine had no effect on the stimulated 86Rb(+)-uptake. Ouabain and HOE 694 also dose dependently inhibited a portion of the basal 86Rb(+)-uptake (about 60% and 20%, respectively), but there was no effect of bumetanide or 4-aminopyridine on the basal 86Rb(+)-uptake. The results show that the Na+/K+ATPase alone mediates the alpah 1-adrenoceptor stimulated increase in potassium uptake in this preparation of ventricular cardiomyocytes isolated from adult rat heart.
Res Commun Mol Pathol Pharmacol 1997 Apr
PMID:The Na+/K+ATPase mediates the alpha 1-adrenoceptor stimulated increase in 86Rb(+)-uptake in isolated ventricular cardiomyocytes from adult rat heart. 917 70

It was the aim of the present study (1) to characterize the influence of Na+/K(+)-ATPase inhibition by the digitalis glycoside ouabain on both spontaneous and nicotine-evoked norepinephrine release from the human heart; and (2) to further investigate the role of glycoside-induced changes in [Na+]i and [Ca2+]i (determined by microfluorimetry) for catecholamine release. The latter experiments were performed in bovine adrenal medullary chromaffin cells (BCC), an established cell culture model for sympathetic nerves. Ouabain (1-1000 mumol/l) exerted a dual effect on norepinephrine release (determined by HPLC) from incubated human atrial tissue: (I) Ouabain induced a concentration-dependent increase in norepinephrine release, that was calcium-independent and almost completely prevented by blockade of the uptake1-carrier by desipramine (1 mumol/l). The characteristics of this release process are consistent with a non-exocytotic mechanism. (II) In addition, ouabain augmented the nicotine-evoked (1-100 mumol/l) calcium-dependent norepinephrine release, which can be considered to be exocytotic. Na+/K(+)-ATPase inhibition also reduced the threshold concentration of nicotine from 10 to 1 mumol/l and it delayed the rapid tachyphylaxis of its norepinephrine releasing effect in human atrial tissue. In BCC, ouabain increased [Na+]i, [Ca2+]i and [3H]-norepinephrine release in parallel. Under calcium-free conditions, not only the ouabain-induced increase in [Na+]i, but also [3H]-norepinephrine release were enhanced. The ouabain-induced [3H]-norepinephrine release was always closely related to changes in [Na+]i, indicating a key role of [Na+]i for this calcium-independent non-exocytotic norepinephrine release. In addition, pretreatment with ouabain (1 mmol/l) augmented the nicotine-evoked (0.1-10 mumol/l) increments in [Na+]i, [Ca2+]i and [3H]-norepinephrine release. As nicotine-induced norepinephrine release depends on an increase in both [Na+]i and [Ca2+]i, these findings are indicative of an ouabain-mediated facilitation of exocytosis. In conclusion, increasing [Na+]i and [Ca2+]i inhibition of Na+/K(+)-ATPase by ouabain triggers non-exocytotic norepinephrine release, and facilitates nicotine-evoked exocytotic norepinephrine release.
J Mol Cell Cardiol 1997 Jun
PMID:Dual effect of digitalis glycosides on norepinephrine release from human atrial tissue and bovine adrenal chromaffin cells: differential dependence on [Na+]i and [Ca2+]i. 922 Mar 47

Both mania and bipolar depression have been associated with decrements in the activity of the sodium and potassium-activated adenosine triphosphatase (Na,K-ATPase) membrane pump. Although the role of this observation in the pathophysiology of bipolar illness is unclear, it has been proposed that this defect could be central to the pathogenesis of the illness. In an effort to test this hypothesis, the authors examined the efficacy of lithium pretreatment in attenuating behavioral changes secondary to acute administration of a single intracerebroventricular (i.c.v.) dose of the Na,K-ATPase-inhibiting compound, ouabain, in the Sprague-Dawley rat. Ouabain (10(-3)M) significantly decreased motor activity in automated activity monitors. Lithium pretreatment for 7 d totally prevented this effect. These preliminary data suggest that i.c.v. ouabain administration in the rat may prove to be a viable animal model for bipolar illness.
Mol Chem Neuropathol 1997 May
PMID:Lithium prevents ouabain-induced behavioral changes. Toward an animal model for manic depression. 927 Oct 6

We showed before that partial inhibition of Na/K-ATPase by non-toxic concentrations of ouabain caused hypertrophic growth of neonatal rat cardiac myocytes, and induced several early- and late-response genes that are markers of cardiac hypertrophy. The aim of this study was to determine if the genes of the alpha-subunit isoforms of Na/K-ATPase were among those regulated by ouabain; and if so, to begin the characterization of the pathways regulating these genes. When neonatal myocytes, expressing alpha1- and alpha3-isoform messages, were exposed to 5-100 micro M ouabain, alpha1 mRNA was not affected, but alpha3 mRNA was decreased in a dose- and time-dependent manner. Ouabain-induced down-regulation of alpha3 mRNA was accompanied by a decrease in alpha3-protein content in these myocytes. There was a significant correlation between ouabain effects on alpha3-repression and skeletal alpha-actin induction; also, ouabain's transcriptional effects on both genes were antagonised by retinoic acid. These findings suggested the association of alpha3 repression with ouabain-induced hypertrophy. Phenylephrine and a phorbol ester, two hypertrophic stimuli that do not inhibit Na/K-ATPase, also down-regulated alpha3 mRNA without affecting alpha1 mRNA, suggesting that alpha3-repression is a common feature of the hypertrophic phenotype in these myocytes. Ouabain-induced repression of alpha3 required the influx of extracellular Ca2+, and was antagonized by inhibitors of protein kinase C, Ca2+-calmodulin kinase, and mitogen-activated protein kinase but not by inhibition of protein kinase A. These data, and prior findings on the mechanisms of hypertrophic effects of phenylephrine and phorbol esters, suggest that transcriptional repression of alpha3 by ouabain and other hypertrophic stimuli involves a common step regulated by a mitogen-activated protein kinase.
J Mol Cell Cardiol 1997 Nov
PMID:Differential regulation of Na/K-ATPase alpha-subunit isoform gene expressions in cardiac myocytes by ouabain and other hypertrophic stimuli. 940 89

The aim of the present study was to evaluate the direct effect of Li+ and Na+-Li+ exchange on protein phosphorylation in rat cerebral cortex slices incubated in Krebs Ringer medium. When Na+ concentration was varied in the incubation medium, either by replacement with Li+ or sucrose, a variable effect on [32P] phosphate incorporation into proteins was observed. Protein phosphorylation in cerebral cortex slices was very low in the absence of Na+, and some dependence of phosphorylating system of neural tissue on extra cellular concentration of Na+ was evident. Lithium was not able to replace sodium as far as protein phosphorylation in cortical slices is concerned. Ouabain was more effective in a Li+ containing medium in inhibiting protein phosphorylation, presumably due to improper functioning of the sodium pump.
Biochem Mol Biol Int 1998 Mar
PMID:Lithium regulation of protein phosphorylation in rat cerebral cortex slices in vitro. 955 10


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