Developmental increase of digitalis receptors in guinea pig heart

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Abstract
The apparent differences of digitalis tolerance in human newborns or young animals and adults may be due to the difference in either, the sensitivity of Na+, K+-ATPase to digitalis, the binding characteristics of the Na+, K+-ATPase receptor sites or the number of receptor sites itself. Sarcolemmal Na+, K+-ATPase enriched membrane preparations from guinea pig hearts of various age groups were investigated for Na+, K+-ATPase activity, the ability of ouabain to inhibit the enzyme and the 3H-ouabain binding characteristics of the receptor sites. There was a continuous developmental increase in Na+, K+-ATPase activity in fetal (45 days fetus, 1.2 μmol Pi·mg−1 protein·h−1) and newborn (2.4 μmol Pi·mg−1 protein·h−1) reaching maturity at the age of 21 to 25 days (9.1 μmol Pi·mg−1 protein·h−1). The ability of digitalis to inhibit the enzyme, however, was same throughout the development with 50% inhibition occurring at 0.1 μmol·litre−1 concentration of ouabain. The sodium stimulated 3H-ouabain binding was saturable and exhibited a single class of receptor sites. The number of digitalis receptor sites increased progressively in fetal (45 days fetus, 2.2 μmol·mg−1 protein) and newborn (9.1 μmol·mg−1 protein) reaching mature levels at the age of 13 to 25 days. The affinity of the Na+, K+-ATPase receptor sites for digitalis (Kd, 8.68 – 9.33 × 10−9 mol·litre−1) remain unchanged during development. The data obtained is consistent with the concept that Na+, K+-ATPase is the receptor site for digitalis and suggests that factors other than the developmental increase in Na+, K+-ATPase may be relevant to explain the age-related differences in digitalis sensitivity.