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Das Problem des zellulären Herzglykosidrezeptors

The problem of the cellular receptor for cardiac glycosides

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Summary

This review concerns the Na+, K+-ATPase as well as the Na+, K+-pump in the intact membrane and the highly specific inhibition of this transport system by cardiac glycosides.

The interaction between glycoside and enzyme and the regulation of the kinetics of glycoside binding by ATP, K+, Na+, Mg2+ and Ca2+ are described.

Emphasis is placed on the significance of the Na+, K+-pump as the pharmacological receptor for cardiac glycosides. The problems encountered and progress made in attempting to correlate the inotropic action of cardiac glycosides with the binding of these drugs to the heart muscle and with the inhibition of the Na+, K+-pump are reported.

Recent results concerning increases of the intracellular Na+ concentration which are obtained by a partial inhibition of the Na+, K+-pump and which are followed by an elevation of the intracellular Ca2+-activity are reviewed.

The discovery of a digitalis-like endogenous activity corresponds to the high specificity of the receptor for cardiac glycosides.

Zusammenfassung

Diese Übersicht beschreibt die Eigenschaften der Na+, K+-ATPase bzw. der Na+, K+-Pumpe in der intakten Membran und die hochspezifische Hemmung dieses Transportenzyms durch Herzglykoside.

Es wird auf die Wechselwirkung zwischen Glykosid und Enzym eingegangen und da bei insbesondere auf die Steuerung der Glykosidbindung durch ATP, K+, Na+, Mg2+ und Ca2+.

Die Bedeutung des Enzyms als wahrscheinlicher pharmakologischer Rezeptor für Herzglykoside wird herausgestellt. Zunächst erfolgt eine Beschreibung der Schwierigkeiten und Fortschritte bei der Herstellung eines Zusammenhanges zwischen positiv inotropem Effekt von Herzglykosiden und deren Bindung an die Na+, K+-Pumpen des Herzmuskels bzw. der Hemmung des Transportsystems durch Herzglykoside.

Es werden neuere Erkenntnisse über die Verknüpfung von der Hemmung der Na+, K+-Pumpe, die zu einer Erhöhung der intrazellulären Na+-Konzentration führt, und der indirekten Erhöhung der intrazellulären Ca2+-Aktivität referiert.

Mitteilungen über den Nachweis einer herzglykosidartigen endogenen Aktivität entsprechen der hohen Rezeptorspezifität für Herzglykoside.

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    H. H. Bodemann

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Bodemann, H.H. Das Problem des zellulären Herzglykosidrezeptors. Klin Wochenschr 59, 1333–1343 (1981). https://doi.org/10.1007/BF01720553

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