Zur Frage der Fixation der Digitaliskörper im tierischen Organismus und besonders deren Verhalten zum Blut

Oppenheimer, Ernst

doi:10.1007/978-3-662-24649-8_1

Cited by 1 publication

(1 citation statement)

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“…Interaction of digitoxin and certain other cardiac glycosides with a constituent of serum has been known since 1913 when Oppenheimer reported that the toxic effects of these compounds on the isolated frog heart were markedly attenuated when they were dissolved in rabbit, ox, or horse serum rather than in Ringer's solution (1). Subsequent investigators (2)(3)(4) demonstrated that the protective action of serum was related to binding of the glycosides by albumin, and that the globulins did not participate in this reaction.…”

Section: Introductionmentioning

confidence: 99%

Binding of digitoxin and some related cardenolides to human plasma proteins

Lukas¹,

Martino²

1969

J. Clin. Invest.

136

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A B S T R A C T Tritium-labeled digitoxin, digitoxigenin, digoxin, and digoxigenin of established purity and chemcal authenticity were used to study the binding of these compounds to human plasma proteins. 97% of digitoxin in plasma was nondialyzable. Continuous flow paper electrophoresis of plasma containing digitoxin and dialysis experiments in which human serum albumin competed for the glycoside with plasma or plasma protein fractions demonstrated that digitoxin was almost exclusively bound by albumin. Equilibrium dialyses revealed that the interaction was characterized by a single binding site on the albumin molecule and an association constant of 9.62 X 10' liter/mole at 370C. At 1VC the association constant was 4.64 X 10' liter/mole. The interaction therefore was endothermic; the gain in enthalpy of 3.5 kcal/mole and the free energy change of -7.06 kcal/ mole was derived from a large change in entropy of 33.8 cal/mole per 'K. The direction of these thermodynamic changes suggested the formation of a hydrophobic bond between digitoxin and albumin. Quenching of the fluorescence of albumin by digitoxin indicated that the conformation of albumin was altered by the binding process.Digitoxigenin, its mono-and didigitoxosides, digoxin, and digoxigenin competed with digitoxn for its binding site on albumin. The affinity of the mono-and didigitoxosides for the site was equal to that of digitoxin, but that of digitoxigenin was only one-third as great. The ability of the digitoxose residues of the glycosides to enhance binding to albumin was also observed with digoxin, Presented in part at the 28th Scientific Sessions of the American Heart Association, Miami Beach, Fla., 16 October 1965.Dr. De Martino was formerly a Postdoctoral Research Fellow of the National Heart Institute.Received for publication 15 November 1968 and in revised form 6 February 1969. which was more extensively bound by the protein than digoxigenin.At concentrations of 2 jg/ml or less in plasma, only 23% of digoxin was bound. Albumin, which interacted with digoxin with an apparent association constant of 9 X 102 liter/mole at 370C, was entirely responsible for the binding. Lowering the temperature from 370 to 1VC decreased the fraction of digoxin bound to albumin by two-thirds.The marked difference in avidity of digitoxin and digoxin for serum albumin is reflected by the higher plasma concentrations, lower rate of urinary excretion, and longer half-time of digitoxin as compared to those of digoxin when these compounds are administered to man.

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Section: Introductionmentioning

confidence: 99%