The cardiac glycoside-receptor system in the human heart

Abstract

Specific binding sites have been demonstrated to exist in the heart for several drugs and hormones such as beta- blocking agents, cardiac glycosides, catecholamines, insulin, glucagon and acetylcholine. The specific binding sites for cardiac glycosides in the human heart have certain properties which make it likely that they are the pharmacological receptors for the therapeutic and toxic actions of digitalis glycosides: they are located in the cell membrane and bind cardioactive steroids reversibly with high affinity half-maximal receptor binding occurs at∼2 nM (∼1·5 ng/ml) for digoxin; potassium decreases receptor affinity, calcium increases it; specific binding of ouabain, digoxin or digitoxin is related to inhibition of (Na ⁺ + K ⁺ )-A TPase activity—which is supposed to be the receptor enzyme for cardiac glycosides. Human left ventricle contains ∼ 15 × 10 ¹⁴ binding sites/g wet weight, right ventricle ∼ 0·9 × 10 ¹⁴ In disease the number of receptors may decrease (hypothyroid states, myocardial infarction) or increase (hyperthyroidism, chronic hypokalaemia). Certain drugs (such as phenytoin) or different temperatures or pH changes cause a change in digitalis-receptor affinity. Thus, the number of receptors and possibly their properties are subject to regulation in clinically relevant situations. Further investigations will probably reveal those pathophysiological states, which allow the explanation of toxicity or digitalis refractoriness.

Receptors, digitalis, binding sites