[Quantitative aspects of specific binding of cardiac glycosides to membrane receptors]

Although the exact mechanism of positive inotropic action of cardiac glycosides is unknown, specific membrane bound proteins with high affinity for this group of drugs have been characterized. These "receptors" for cardiac glycosides have been measured quantitatively in cardiac tissue of humans and several species as well as in other tissues. The occupation of receptors by cardioactive steroids has been found to agree quantitatively with the drug effects in respect to inhibition of (Na+ + K+)-ATPase and in respect to positive inotropy (these experiments were performed in electrically stimulated contracting cardiac muscle). Changes in receptor concentration or receptor properties have been observed in hyperthyroidism, chronic hypokalaemia, thalassaemia or in acutely changed serum concentrations of K+, Ca++ and several drugs. These changes may be of great significance in patients treated with cardiac glycosides as their effects are not reflected by the serum concentration of cardiac glycosides. The understanding of drug-receptor-interactions on the molecular level--especially under the pathological conditions in the patient--will increase our diagnostic and therapeutic knowledge.