Influence of digitalis and diuretics on ouabain binding sites on human erythrocytes

Summary It has been reported that during chronic treatment with digitalis, the number of digitalis binding sites is increased in human erythrocytes 22]. From this finding a tachyphylaxis for cardiac glycosides has been postulated. We reinvestigated this problem in several groups of patients.The number of³H-ouabain binding sites per erythrocyte in control persons (group I) was 214±60,n=43 (x±SD). The dissociation constant (K_D) was 1.8±0.5 nM. Thirteen patients (group II) taking cardiac glycosides only, for at least 6 months, had 281±99 (p<0.05) ouabain binding sites per single red cell, K_D=1.8±0.7 nM. Group III (34 patients) took digitalis for more than 6 months and diuretics for at least 3 months (352±126 (p<0.001), K_D=1.6±0.6). Twenty-three of these (group IV) were taking a combination with K⁺-saving diuretics (336±194 (p<0.01), K_D=1.6±0.5) and (group V, 11 patients) a combination with K⁺-losing diuretics (462±133 (p<0.001), K_D=1.4±0.4). Nine patients (group VI) had a chronic hypokalemia, mainly due to taking furosemide (437±98 (p<0.001), K_D=1.5±0.4). Four control persons took 50 mg hydrochlorothiazide daily for more than 4 months without measurable K⁺-losses and without changes in ouabain binding sites.It is concluded from these findings that diuretic treatment with chronic hypokalemia in addition to digitalis is accompanied by a significant increase in ouabain binding sites in human red cells. Although the difference between control persons and those taking cardiac glycosides only, is statistically significant (p<0.05), the biological relevance is questionable because of considerable overlap of the values. Receptor affinity was unchanged under all circumstances. A change in the number of ouabain binding sites — if occurring also in the heart — may go along with an altered digitalis sensitivity.Supported by the DFG (Er 65/4-3)