Über die Identität der Ionenpumpen-ATPase in der Zellmembran des Herzmuskels mit einem Digitalis-Rezeptorenzym

Repke, K.; Portius, H. J.

doi:10.1007/bf02150643

Cited by 134 publications

(16 citation statements)

References 61 publications

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“…These experiments and those analysing the interaction of ouabain with the Na-K-adenosine triphosphatase (Schwartz, Allen & Harigaya, 1969), suggest that some part of the sodium pump could act as a digitalis receptor, confirming the hypothesis of Repke & Portius (1963). It was therefore of interest to compare the apparent affinity constant determined by measuring either the inotropic effect or the inhibition of the sodium pump to the affinity constant estimated by analysing 3H-cardiac glycoside uptake, as a similarity of these constants would be an argument in favour of the existence of only one receptor for digitalis action.…”

Section: Introductionsupporting

confidence: 53%

The uptake of cardiac glycosides in relation to their actions in isolated cardiac muscle

Godfraind

Lesne

1972

British J Pharmacology

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Summary1. The uptake of 3H-digitoxin, 3H-ouabain and 3H-dihydro-ouabain by isolated guinea-pig atria has been studied and compared with the inhibition of the sodium pump and with the inotropic effect.2. Analysis of the curve relating the uptake of digitoxin and ouabain at equilibrium to the bath concentration enabled a non-saturable and a saturable binding site to be distinguished. 3. The uptake of inactive doses of dihydro-ouabain was only by a nonsaturable mechanism. 4. The uptake of labelled digitoxin and ouabain was reduced in the presence of another glycoside. The amount of bound glycoside was nearly equivalent to the estimated non-saturable uptake. 5. The uptake was reduced at 40 C to the clearance of the non-saturable site. 6. ED50 of digitoxin and of ouabain for inhibition of the sodium pump were measured and compared to the ED50 for inotropic effect and to the concentrations producing a half-saturation of the saturable binding site. 7. It is concluded that binding to the saturable site may be responsible for the cardiac actions of the glycosides.

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Section: Introductionsupporting

confidence: 53%

The uptake of cardiac glycosides in relation to their actions in isolated cardiac muscle

Godfraind

Lesne

1972

British J Pharmacology

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“…The sodium pump is inhibited by ouabain (e.g. Repke & Portius, 1963), and it has been postulated that there are two phases in the glycoside's action. Baker & Willis (1972) refer to a primary phase that is a consequence of Na+-K+-ATPase inhibition and is concentration-dependent but does not follow simple first-order kinetics.…”

Section: Discussionmentioning

confidence: 99%

Effects of ouabain on carotid body chemoreceptor activity in the cat.

McQueen¹,

Ribeiro²

1983

The Journal of Physiology

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SUMMARY1. The effects of infusions of ouabain on chemoreceptor activity recorded from the peripheral end of a sectioned carotid sinus nerve were studied in cats anaesthetized with pentobarbitone.2. Ouabain caused a marked increase in chemoreceptor discharge followed by a decline in discharge to frequencies near or below the pre-ouabain level; during the latter period further administration of ouabain had no effect.3. Infusion of ouabain during hypoxia further increased the chemoreceptor discharge, but this effect was short-lasting.4. On intracarotid administration ouabain was less effective in cats with the ganglioglomerular (sympathetic) nerves cut, whereas on intravenous administration no significant difference was observed. Following intravenous administration of ouabain the chemoreceptor peak discharge occurred with dose levels similar to those needed to cause cardiac arrhythmias, but following intracarotid administration the chemoreceptor discharge peaked at doses about 40 % of those causing arrhythmias.5. During ouabain-induced excitation the stimulatory action of NaCN, CO2-equilibrated Locke solution and acetylcholine was potentiated, as was the chemoinhibition induced by dopamine. During the post-excitatory period the responses evoked by these substances were reduced or abolished.6. Neither mecamylamine, a nicotinic antagonist, nor physostigmine, an anticholinesterase, affected the response of the carotid chemoreceptors to ouabain.7. The major finding of this study was that ouabain initially 'sensitizes' the carotid body chemoreceptors and then 'desensitizes' them. The most likely mechanism responsible for these effects is the well established Na+-K+-ATPase-inhibiting property of ouabain.

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“…The Mg2"-dependent, Na+ and K+-activated adenosine triphosphatase (Na, K-ATPase) is generally considered to represent the receptor for cardiac glycosides (Repke & Portius, 1963;Schwartz, Lindenmayer & Allen, 1975;Lullmann & Peters, 1979). Recently, several cardiac glycoside derivatives were obtained by chemical modification, e.g.…”

Section: Introductionmentioning

confidence: 99%

Electrophysiological studies of some semisynthetic cardiac glycoside derivatives in isolated papillary muscle of the guinea‐pig

Lüllmann

Niehus

Pulss

et al. 1983

British J Pharmacology

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1 The effects of digitoxin, 3a-methyl-digitoxigenin-3p-monoglucoside (3a-MDM), 3a-methyldigitoxigenin (3a-MD), proscillaridin, 4, 5-methylene-procillaridin (4, 5-MP), and 3p-hydroxy-4, 5-methylene-A, B-trans-scillarenin (3p-HMTS) on force of contraction and on the transmembrane action potentials were examined in isolated papillary muscles of guinea-pigs. 2 All derivatives exhibited the typical cardiac glycoside effects: i.e. they increased the force of contraction and shortened the action potential duration at 20% (plateau phase) and 90% of repolarization. With digitoxin, 3P-HMTS and 4, 5-MP a transient prolongation in action potential duration was observed at the lower concentrations. The action potential amplitude and the resting membrane potential were reduced consistently only with the higher concentrations used.3 The onset of the positive inotropic effects of 3a-MDM, 3x-MD and 3P-HMTS was more rapid than that of digitoxin and proscillaridin. The increment in contractile force reached a maximum well before the full shortening effect on the action potential duration had developed. The shortening of the action potential is thought to be responsible for the biphasic nature of the positive inotropic effect. 4 With 3a-MD and 3a-MDM even toxic effects, e.g. increase in baseline tension, were completely reversible after washing in drug-free solution. 5 The dose-response curves for the positive inotropism can only be compared reliably once the equilibrium of drug action has been established. This steady state is probably reflected by the development of the full shortening in action potential duration.

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Über die Identität der Ionenpumpen-ATPase in der Zellmembran des Herzmuskels mit einem Digitalis-Rezeptorenzym

Cited by 134 publications

References 61 publications

The uptake of cardiac glycosides in relation to their actions in isolated cardiac muscle

The uptake of cardiac glycosides in relation to their actions in isolated cardiac muscle

Effects of ouabain on carotid body chemoreceptor activity in the cat.

Electrophysiological studies of some semisynthetic cardiac glycoside derivatives in isolated papillary muscle of the guinea‐pig

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