Inhibitory effects of cardiac glycosides and adrenal steroids on amino acid transport

The cardiac glycosides, ouabain, scillaren, and scilliroside, inhibit the transport of α-aminoisobutyric acid (AIB) into isolated intact rat diaphragm when present in the medium at a concentration of 10–3 m. Lower concentrations of the glycosides do not inhibit AIB uptake, but cause marked shifts in the distribution of sodium and potassium in the diaphragm. Decreasing or increasing the concentration of potassium in the medium does not markedly alter the ability of ouabain to inhibit amino acid transport, although high extracellular potassium alone causes inhibition of AIB uptake. Ouabain does not alter the ATP content of the diaphragm. For these and other reasons which are discussed, the inhibitory effects of cardiac glycosides on AIB transport appear to be independent of their effects on ion transport, and not related to a possible action on limiting the ATP supply of the cell. It is suggested that their action on amino acid transport may be related to their structural similarity to steroid hormones, which also inhibit amino acid transport. Corticosterone, deoxycorticosterone, and aldosterone inhibit AIB transport when present in vitro at concentrations in the micromolar range. The possible physiological significance of this in vitro effect of adrenal steroid hormones is discussed.