BIOCHEMICAL STUDIES ON MECHANISM OF THE ACTION OF CARDIAC GLYCOSIDES

REPORT 3: INFLUENCES OF CARDIAC GLYCOSIDES ON OXIDATIVE PHOSPHORYLATION IN PIG HEART MITOCHONDRIA

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The effect of cardiac glycosides on the metabolism of cardiac muscles has been a leading subject of study from both pharmacological and clinical points of view in association with the clarification of a mechanism of action of cardiac glycosides and of digitalis intoxication. Particularly, the influence of cardiac glycosides on the metabolism of energyrich phosphate compounds, which are regarded as sources of the contractile energy of cardiac muscles, are now studied attentively by many of researchers. Many investigations have been made of the effect of cardiac glycosides on oxidative-phosphorylation in order to inquire into their effect on the production of energy-rich phosphate compounds in cardiac muscles. It was reported that cardiac glycosides produce no effect on oxidativephosphorylation in both heart homogenates ?? Wollenberger (1), Herrmann (2), and Reiter and Barron (3) ?? and mitochondria ?? Langemann (4) and Kimura (5) ?? . Of late, Goldschmidt and Lamprecht (6) have found that k-strophanthin has an uncoupling effect in heart sarcosomes. In the preceding paper the author showed that ouabain and digitoxin only in high concentrations produced a slight uncoupling effect in guinea pig cyclophorases (7).
As described above, the general current of opinion in this field is that cardiac glycosides have no effect on oxidative-phosphorylation. Some of workers, however, express the opinion that they have an uncoupling effect. This discrepancy in opinion suggests the necessity of further investigations. In addition to this, most of those workers tended to carry out their experiments with only one of cardiac glycosides and, on the basis of the results obtained, to discuss universally an effect of cardiac glycosides on oxidative-phosphorylation.
Therefore, the author attempted to observe an effect of g-strophanthin, desacetyl lanatoside C (cedilanid), digoxin, digitoxin, two kinds of water-soluble cardiac principles extracted from digitalis purpurea at this department, and digitoxigenin on oxidativephosphorylation in pig heart mitochondria, and to draw the general conclusion on the effect of cardiac glycosides on oxidative-phosphorylation in cardiac muscles.