Summary
The recent synthesis of bufenolides permits the introduction into the lactone moiety of a latently reactive group suitable to localize exactly the binding site of the lactone ring of cardioactive steroids on the sodium/potassium pump. For this purpose it is essential to demonstrate that the bufenolides are cardioactive. In the present paper the effect of the bufenolide 22,23-dihydrobufalin on contraction and active sodium/potassium transport is studied by means of electrophysiological methods in sheep cardiac Purkinje fibres. The results are compared to the corresponding actions of some other cardioactive steroids.
22,23-dihydrobufalin exerts a reversible positive inotropic effect. Simultaneous measurements of intracellular sodium activity and membrane current in voltage clamped fibres reveal an inhibition of the sodium/potassium pump by 22,23-dihydrobufalin in the concentration range tested (10−7 to 5·10−5 mol/1). An apparent equilibrium dissociation constant KD′ of about 10−6 mol/l is derived for the drug — sodium/potassium pump interaction. The KD value for bufalin is smaller, whereas the value for ouabain is comparable. The KD′ value estimated for dihydroouabain is slightly larger.
It is concluded that 22,23-dihydrobufalin shares important characteristics with cardioactive steroids. Thus, bufenolides are probably useful tools for an exact localization of the lactone binding site on the cardiac sodium/potassium pump.
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This work was supported by the Deutsche Forschungsgemeinschaft (Forschergruppe “Konzell”)
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Glitsch, H.G., Pusch, H. & Zylka, C. The action of 22,23-dihydrobufalin and other cardioactive steroids on contraction and active sodium/potassium transport of sheep cardiac Purkinje fibres. Naunyn-Schmiedeberg's Arch Pharmacol 342, 598–604 (1990). https://doi.org/10.1007/BF00169051
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DOI: https://doi.org/10.1007/BF00169051