Influence of Cardiac Glycosides on their Receptor

Erdmann, Erland

doi:10.1007/978-3-642-68163-9_15

Cited by 35 publications

(15 citation statements)

References 114 publications

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“…Positive inotropy of cardiac g!ycosides is correJated with some 20-30% of oeeupancy of cardiac glycoside receploTS in the heart [13]. Within Ihis range, changes in Na + -and K --contents in the heart sho uld be small or even absent (Fig.…”

Section: Ckvummentioning

confidence: 96%

“…Applying the criteria for speeifi e and non specific binding of cardiac glycosides to isalated eell me mo branes [13] , descriptio n of (lH)-ouabain binding in intaet myocardial musele cells is possible : binding of ouabain to specifie binding sites is abolished by heat denaturation of the cells, by addition of excesss of unlabeled ouabain , and in the presence of high K~ concentrations. The remaining amo unt of eH)-radioactivity bound to the cells after applying these procedures the n represents non speciti.c binding of e H)-o uabain.…”

Section: Specijic E H )-Ouabain Bindingmentioning

confidence: 99%

“…This receptor is part of the (Na" + K")-ATPase, the biochemieal equivalent of the sodium pump (for review see [13]). Though the sodium pump apparcntly represents the rcceptor.…”

mentioning

confidence: 99%

“…as the cardiac glycoside receptor is located on the outer surface ofthe cell membrane (13). il should be easily accc:ssible in inlact cells (or radioactively labeled ligands .…”

mentioning

confidence: 99%

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Cardiac glycoside receptors in cultured heart cells—I. characterization of one single class of high affinity receptors in heart muscle cells from chick embryos

Werdan

Wagenknecht

Zwißler

et al. 1984

Biochemical Pharmacology

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Section: Ckvummentioning

confidence: 96%

Section: Specijic E H )-Ouabain Bindingmentioning

confidence: 99%

“…This receptor is part of the (Na" + K")-ATPase, the biochemieal equivalent of the sodium pump (for review see [13]). Though the sodium pump apparcntly represents the rcceptor.…”

mentioning

confidence: 99%

“…as the cardiac glycoside receptor is located on the outer surface ofthe cell membrane (13). il should be easily accc:ssible in inlact cells (or radioactively labeled ligands .…”

mentioning

confidence: 99%

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Cardiac glycoside receptors in cultured heart cells—I. characterization of one single class of high affinity receptors in heart muscle cells from chick embryos

Werdan

Wagenknecht

Zwißler

et al. 1984

Biochemical Pharmacology

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“…Although most studies on the binding of cardiac glycosides result in a saturable binding which involves one single class of binding sites (for references see Wallick et al, 1979;Erdmann, 1981), recent reports on different species and tissues have focussed on the possible existence of at least two populations of cardiac glycoside binding sites (e.g. Inagaki et al, 1974;Fricke & Klaus, 1977;Heller & Beck, 1978;Sweadner, 1979;Erdmann et al, 1980;Lazdunski et al, 1983).…”

Section: Discussionmentioning

confidence: 99%

Erythrosin B inhibits high affinity ouabain binding in guinea‐pig heart Na⁺‐K⁺‐ATPase without influence on cardiac glyoside induced contractility

Fricke

1985

British J Pharmacology

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Binding of [3H]‐ouabain to guinea‐pig heart membranes enriched in Na+‐K+‐ATPase revealed two different cardiac glycoside binding sites. High affinity binding was obtained at a KD = 2.2 × 10−7 mol 1−1 (Bmax = 16.8 pmol ouabain mg−1 protein) whereas low affinity ouabain binding occurred at a KD > 10−6 mol 1−1. To discover whether the two ouabain binding sites are functional in guinea‐pig heart muscle, erythrosin B, an inhibitor of the high affinity ouabain binding in rat brain tissue, was tested in guinea‐pig isolated heart muscle preparations. Erythrosin B proved to be a potent inhibitor of the Mg2+(Na+)‐dependent‐, as well as Na+‐K+‐activated ATPase (ID50 = 9 × 10−6 mol 1−1). Contractility of guinea‐pig isolated papillary muscles, however, was not influenced by erythrosin B in concentrations up to 1 × 10−5 mol 1−1. Only very high concentrations (4 × 10−4 mol 1−1) resulted in a slightly negative inotropic effect (about 20%). Erythrosin B dose‐dependently inhibited [3H]‐ouabain binding to the Na+‐K+‐ATPase (KD = − 3.6 × 10−6 mol 1−1). In a concentration of 1 × 10−5 mol 1−1 the dye abolished high affinity [3H]‐ouabain binding without affecting the low affinity binding sites. In contrast, in guinea‐pig isolated atria, no functional antagonism between erythrosin B (5 × 10−5 mol 1−1) and ouabain was observed. As there is a coincidence between the high affinity binding (KD = 2.2 × 10−7 mol 1−1) and the concentration for half maximum inotropic effects of ouabain (ED50 = 1.6 × 10−7 mol 1−1), the lack of effect of erythrosin B on ouabain‐induced inotropy may be caused by an inaccessibility of the dye to the (internal) ATP‐site of the Na+‐K+‐ATPase.

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Digitalisforschung in Berlin‐Buch – Rückblick und Ausblick

et al. 1995

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Der Arzt William Withering führte 1785 mit seinem Buch „An Account of the Foxglove and some of its Medical Uses”︁ Präparate aus Digitalisblättern in die Therapie der Wassersucht (des Herzversagens) ein und erklärte: „The following remarks consist partially of matter of fact, and partially of opinion. The former will be permanent; the latter must vary with the detection of error, or the improvement of knowledge. I hazard them with diffidence, and hope they will be examined with candour.”︁ Diese Bemerkungen sind hier vom Seniorautor angeführt, da er die Schwierigkeit sieht, einen ausgewogenen Bericht über sein lebenslanges Forschungsprojekt zur Digitalis‐Weiterentwicklung zu bieten. Seine Entscheidung, sich der Digitalisforschung zu widmen, entstand am Krankenbett, an dem er als Arzt die furchtbaren Endstadien des Herzversagens erlebte, in denen für die Kranken keine wirkliche Hilfe mehr möglich ist. Unglücklicherweise paßte dieses Vorhaben nicht in das vom Wissenschaftsministerium der DDR dekretierte Forschungsprogramm, so daß er das Digitalisprojekt zugunsten von Biomembran‐Untersuchungen einstellen sollte. Glücklicherweise entging er dem Verdikt durch Etikettierung der digitalisartig wirkenden Steroide als chemische Sonden für die Zellmembran‐lokalisierte Na+/K+ ‐transportierende ATPase, die er gerade als den Digitalisrezeptor erkannt hatte. Über die Arbeit der Autoren wird hier erstmals im Zusammenhang berichtet. Ziel des Überblicks ist, die Forschung für die Lösung einer großen Aufgabe zu fördern: die Entwicklung von Steroidwirkstoffen zur Verhinderung und Heilung der Herzinsuffizienz.

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Influence of Cardiac Glycosides on their Receptor

Cited by 35 publications

References 114 publications

Cardiac glycoside receptors in cultured heart cells—I. characterization of one single class of high affinity receptors in heart muscle cells from chick embryos

Cardiac glycoside receptors in cultured heart cells—I. characterization of one single class of high affinity receptors in heart muscle cells from chick embryos

Erythrosin B inhibits high affinity ouabain binding in guinea‐pig heart Na⁺‐K⁺‐ATPase without influence on cardiac glyoside induced contractility

Digitalisforschung in Berlin‐Buch – Rückblick und Ausblick

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Influence of Cardiac Glycosides on their Receptor

Cited by 35 publications

References 114 publications

Cardiac glycoside receptors in cultured heart cells—I. characterization of one single class of high affinity receptors in heart muscle cells from chick embryos

Cardiac glycoside receptors in cultured heart cells—I. characterization of one single class of high affinity receptors in heart muscle cells from chick embryos

Erythrosin B inhibits high affinity ouabain binding in guinea‐pig heart Na+‐K+‐ATPase without influence on cardiac glyoside induced contractility

Digitalisforschung in Berlin‐Buch – Rückblick und Ausblick

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Erythrosin B inhibits high affinity ouabain binding in guinea‐pig heart Na⁺‐K⁺‐ATPase without influence on cardiac glyoside induced contractility