title: Developmental increase of digitalis receptors in guinea pig heart.
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 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.
mesh_terms: 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
chemical_list: D004071:Digitalis Glycosides; D011955:Receptors, Drug; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase