Developmental increase of digitalis receptors in guinea pig heart.
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 mumol Pi . mg-1 protein . h-1) and newborn (2.4 mumol Pi . mg-1 protein . h-1) reaching maturity at the age of 21 to 25 days (9.1 mumol 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 mumol . 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 pmol . mg-1 protein) and newborn (9.1 pmol . 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 x 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.
D000818:Animals; D004071:Digitalis Glycosides / Q000378:metabolism*; D004361:Drug Tolerance; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000254:growth & development*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010042:Ouabain / Q000378:metabolism; D011955:Receptors, Drug / Q000378:metabolism / Q000502:physiology*; D012508:Sarcolemma / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism
D004071:Digitalis Glycosides; D011955:Receptors, Drug; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase