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)

The effects of topically applied ouabain, epinephrine and bicuculline on the electrocorticographic activity were studied in unanesthetized cats with high cervical transection. Ouabain in a concentration of 25 X 10(-6) induced single intermittent spikes or paroxysms lasting for about 4-10 min. A 5% solution of bicuculline also induced paroxyms which lasted for many hours and were suppressed by topical epinephrine. Ouabain paroxysms became more vigorous when applied after epinephrine and bicuculline. Topical epinephrine dimished the ouabain discharges and the click evoked cortical responses. It is suggested that the epileptogenic activity of ouabain and bicuculline and its antagonization by epinephrine can be accounted for by the antagonistic effects of these agents on the electrogenic ion pumps such as inhibition and stimulation of the (Na + K) ATPase activity, respectively.
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PMID:Electrocorticographic effects of topically applied ouabain, epinephrine and bicuculline. 86 39

1 The influence of ouabain (0.4 muM) on contractile force and cellular Na and K concentrations was investigated in isolated left atria of the guinea-pig at rest and at different beat frequencies. Simultaneously the binding of ouabain to the tissue was determined.2 Strict dependence of rates of onset of positive iontropic action and of binding of ouabain on beat frequency are limited to conditions where no alterations of cellular Na and K concentrations occur. A correlation was observed between sodium flux per unit time and the development of positive inotropism and binding to the receptors of ouabain.3 Ouabain exerts its positive inotropic effect without affecting the intracellular Na and K concentrations in spite of the fact that under these conditions even the majority of binding sites, i.e. Na-K-adenosine triphosphatases (Na-K-ATPases), are occupied by the drug. The positive inotropic effect may be explained by a ouabain-induced conformational alteration of the Na-K-ATPase which leads to structural alterations of the plasmalemma connected with an increased availability of coupling calcium.4 Increasing the frequency of stimulation over a critical value, which appears to be determined by an overloading of the Na pump, induces a decrease in contractile force, cellular accumulation of Na and loss of K, and eventually contracture.5 The rate of binding of ouabain appears to depend on the actual concentration of particular conformations of the Na-K-ATPase with high affinity for ouabain. These conformations transiently occur during a pumping cycle and their concentration may therefore be dependent on the frequency of cycling which in turn is determined by the frequency of contraction.6 Ouabain can easily be washed out from the tissue irrespective of the condition of the muscle. If, however, the intracellular Na and K homeostasis is impaired, the inhibition of the pump persists even if ouabain is released from the binding sites upon wash-out. It is suggested that the inhibition of the pump is maintained by an increased intracellular Ca ion concentration and a depletion of ATP.7 A kinetic model is proposed for the interaction between cardiac glycosides and the Na-K-ATPase in intact heart muscle cells.
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PMID:Interdependence of ion transport and the action of quabain in heart muscle. 91 8

1. Changes in water and ion contents of renal cortical slices from rat, rabbit and guinea-pig incubated in medium of a half normal osmolarity were followed over 60 min incubation at 25 degrees C.2. Metabolizing slices gained water and lost sodium and chloride but not potassium. These changes reflected in part changes in cellular composition, and were complete within 5 min. A new steady-state was then maintained for a further 55 min.3. Slices initially incubated for 60 min with ouabain, also lost sodium and chloride when transferred to the hyposmotic medium but did not, in the first minutes, lose any further potassium. Ouabain, in concentrations sufficient to produce maximal inhibition of the Na-K ATPase, did not cause additional cellular swelling in the hyposmotic medium.4. The results offer no support for the claim that cellular volume in metabolizing renal cortical cells exposed to hyposmotic media is regulated by loss of cellular potassium. They suggest that under such conditions the regulation of volume involves the same ouabain-insensitive mechanism as is seen in cells incubated in isosmotic medium.
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PMID:The regulation of cellular volume in renal cortical slices incubated in hyposmotic medium. 94 46

Induction of erythroid differentiation in ouabain-resistant murine erythroleukemia cells by ouabain is reported. Ouabain induction results in the appearance of hemoglobin-containing cells 12-24 hr earlier than induction of the same clone by dimethyl sulfoxide. The levels of globin mRNA after ouabain induction are similar in amount to the globin mRNA levels observed after induction by dimethyl sulfoxide. The concentration of ouabain required to induce hemoglobin synthesis depends upon the K+ ion levels in the culture medium. Lowering the extracellular K+ ion concentration 2-4 fold reduced by 10-40 fold the ouabain concentration necessary for the induction of hemoglobin synthesis. In low K+ medium (1.8 mM), ouabain is an effective inducer of hemoglobin synthesis at a concentration of 0.02 mM. This K+ effect is specific for ouabain induction, since induction by other inducers, such as dimethyl sulfoxide and dimethyl acetamide, does not exhibit this marked sensitivity to the levels of K+ ions in the culture medium. These results suggest that the binding of ouabain to the plasma membrane enzyme, Na/K ATPase, is required for the induction of erythroid differentiation by ouabain. A small but significant proportion of wild-type, ouabain-sensitive cells also can be induced by ouabain, below ouabain concentrations that are toxic to these cells. The observation that the binding of ouabain to the Na/K ATPase induces hemoglobin synthesis suggests that changes in the intracellular concentration of K+ ions may be involved in the control of erythroid differentiation in Friend erythroleukemic cells.
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PMID:Induction by ouabain of hemoglobin synthesis in cultured Friend erythroleukemic cells. 99 Dec 69

Effects of three cardiac glycosides on the accumulation of 3H-1-noradrenaline (3H-1-NA) by slices of heart and spleen were studied. Ouabain, digitoxin and digoxin, all produced a concentration dependent inhibition of 3H-1-NA uptake in both types of tissue slices. The maximum amount of 3H-1-NA accumulated as well as the rate of uptake was decreased. Digitoxin and ouabain were equipotent; however, digoxin was significantly less potent. Tissues from different mamalian specis did not exhibit the same degree of sensitivity to the inhibitory effect of cardiac glycosides on 3H-1-NA accumulation. Dogs were most sensitive and guinea-pigs an order of magnitude less sensitive. Rats were least sensitive by roughly two orders of magnitude when compared with guinea-pigs. The relationship of the effect of digitalis on 3H-1-NA accumulation to digitalis-induced cardiac arrhythmias is discussed. Finally, the pattern of species sensitivity found here is compared with that observed in relation to inhibition of Na+-K+-ATPase by cardiac glycosides.
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PMID:Differential species sensitivity to the inhibitory effect of cardiac glycosides on 3H-1-noradrenaline accumulation by tissue slices. 101 19

Cardiac glycosides which inhibit Na/K-ATPase (ouabain, scilliroside, scillirosidin) as well as heparin and histamine were infused into a cannulated branch of the middle cerebral artery or by isolated head perfusion in cats and dogs. Ouabain permeating the blood-brain barrier (BBB) caused the same selective swelling of astrocytes and of certain presynaptic elements as after direct application to the brain tissue. The other cellular elements of brain tissue and the vascular endothelium did not react, although the latter was exposed to the highest drug concentrations (about 10-3 M ouabain). By the swelling about one third of the capillaries became more or less constricted accompanied by an increase in endothelial vesiculation and in the number of osmiophilic inclusions in all cells of the vascular wall and of the pericapillary tissue. Osmiophilic material resembling plasma proteins occured in widened intercellular clefts indicating an increased BBB permeability after survival times (40 min). In contrast to the capillaries some terminal vessels are dilated which may correspond to shunt vessels causing an inhomogeneous, even increased cerebral blood flow after ouabain. Scilliroside and scillirosidin cause essentially the same changes as ouabain, but of smaller intensity and extent. In the present study, neither histamine nor heparin caused any structural change of the vessels or brain tissue.
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PMID:Cerebrovascular ultrastructural alterations after intra-arterial infusions of ouabain, scilla-glycosides, heparin and histamine. 116 96

1. The influence of ouabain on the tertiary structure of cardiac plasmalemmal proteins was investigated by means of circular dichroism measurement. Purified plasmalemmal microsomes were obtained by sucrose gradient centrifugation. The CD-spectra of the membranal proteins were shifted to the red and the amplitudes were smaller than those of the same proteins after solubilization. 2. Ouabain induced an increase of the ellipticity bands at 210 and 222 nm of about 50% above the level yielded with microsomes after sonication. At 222 nm ouabain exhibited the half maximum effect at a concentration of 5 X 10(-9) M. The effect could, however, only be exerted if the inside of the microsomes was exposed to ouabain by sonication, thus reflecting the inside-out nature of the plasmalemmal microsomes. 3. The high specificity of the ouabain effect was underlined by the following experiments: a) Dihydroouabain, a much less cardioactive derivative of ouabain proved to be ineffective in corresponding concentrations, b) ouabain had no influence upon the CD spectrum of microsomes derived from cardiac sarcoplasmic reticulum, c) a detergent-like action of ouabain underlying the observed effect can be excluded since highly active tensides, i.e. desoxycholate and dodecylsulfate, only influence the CD spectra at concentrations exceeding 10(-3) M, d) electronmicrographs of microsomes exposed to ouabain demonstrated no alteration of either the appearance or size of the microsomes. 4. The magnitude of the observed ouabain effect indicates that a large portion of the membrane-bound proteins is involved. The number of binding sites and their isolated structural alteration induced by ouabain are not sufficient to account quantitatively for the enhanced amplitudes of the CD spctra. This suggests that ouabain evokes structural changes of membrane proteins different from actual binding sites. It seems, therefore highly improbable that changes of the Na-K-ATPase present in the plasmalemmal microsomes are responsible for the observed effect.
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PMID:Influence of ouabain and dihydroouabain on the circular dichroism of cardiac plasmalemmal microsomes. 117 65

We have previously investigated the normal characteristics of thiamine intestinal transport in rats and found that a very low concentrations (0.06 to 2.0 muM) thiamine transport is a saturable, carrier-mediated, active process while at high concentrations (greater than 2.0 muM) transport proceeds by simple diffusion. The present studies were undertaken to characterize the effect of ethanol on thiamine transport. Intact isolated loops were used to measure rates of 35S-thiamine hydrochloride absorption into the circulation in vivo, and everted jejunal segments to measure net transmural flux, unidirectional uptake, and cellular exit of 14C-thiamine hydrochloride in vitro. Intragastric administration of ethanol (50 to 750 mg. per 100 grams of weight) reduced absorption of low thiamine concentration in vivo to 65.44 per cent of control value. A similar inhibition was noted after intravenous ethanol. Once attained, the inhibition of thiamine absorption was not related to the ethanol dose or to ethanol concentration in the blood or in the intestinal lumen; this inhibition was reversible. In contrast, ethanol did not affect absorption of high concentrations of thiamine. These findings were confirmed by the in vitro results. In transmural flux studies, the movement of low, but not high, thiamine concentration against a concentration gradient was inhibited by ethanol, so that the normal serosal/mucosal ratio of 1.5 was reduced to 1.0. Ethanol did not affect unidirectional uptake into the mucosa of either low or high thiamine concentrations, but blocked cellular exit of low thiamine concentrations from the cells into the serosal compartment. Exit of high thiamine concentrations was not affected. Ouabain, like ethanol, markedly reduced cellular exit but did not influence uptake of low thiamine concentrations. The present studies suggest that ethanol adversely affects the active, but not the passive, component of thiamine transport. Moreover, ethanol appears to block thiamine exit from the cells but does not affect cellular uptake of thiamine. The similarity to ouabain action suggests that ethanol may impair active thiamine transport by inhibiting Na-K ATPase activity.
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PMID:Thiamine transport across the rat intestine. II. Effect of ethanol. 118 39

Ouabain exhibits a dose-dependent choleretic effect in the isolated perfused rat liver. Its uptake from the perfusate into the liver is maintained against a concentration gradient and becomes clearly saturated at higher perfusate concentrations. A low extracellular sodium concentration inhibits the rate of ouabain transfer into liver cells, resulting in a marked decrease of the maximal transport rate. Dibucaine completely abolishes the uptake of the glycoside by the isolated liver. Determination of Na-22 tracer fluxes suggests that ouabain uptake is accompanied by a net flux of sodium into the cell, which seems to be due to a cotransport of sodium with ouabain rather than to the inhibition of the sinusoidal Na+ -K+ -ATPase. Sodium introduced into the cell in this way apparently is extruded into the bile canaliculi. The increase of isotonic bile flow, which is simultaneously observed, points to a dilution of the canalicular sodium gradient by water and electrolytes through an intercellular pathway. Our results present further evidence that bile secretion is controlled by transcellular sodium movements.
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PMID:Ouabain-mediated sodium uptake and bile formation by isolated perfused rat liver. 126 18

ATPase activity was measured in samples of freshly dissected rabbit ciliary epithelium. The epithelium was ruptured in distilled water, frozen briefly, and incubated at 37 degrees C in a buffer containing 100 mM NaCl and 32P-labeled adenosine triphosphate (ATP). The rate of ATP hydrolysis by the epithelium was linear for as long as 45 min. Ouabain (1 mM) reduced the ATP hydrolysis rate by approximately 50%. When the epithelium was preincubated for 10 min. in the presence of 1 mM dibutyryl cyclic adenosine monophosphate (cAMP), the ouabain-sensitive (Na,K-ATPase) activity was diminished; ouabain-insensitive ATPase activity was not reduced. Preincubation of the epithelium with forskolin with isobutylmethylxanthine also reduced ouabain-sensitive ATPase activity. These observations suggest that the ciliary epithelium may have a mechanism for short-term modulation of Na,K-ATPase activity by cAMP. Such a mechanism could be linked to the ability of cAMP-dependent protein kinase to reduce Na,K-ATPase activity in the tissue.
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PMID:The influence of cyclic AMP upon Na,K-ATPase activity in rabbit ciliary epithelium. 131 Sep 56


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