The difference in sensitivity to cardiac steroids of (Na++K+)-stimulated ATPase and amino acid transport in the intestinal mucosa of the rat and other species.

1. The effect of various cardioactive steroids on the activity of a microsomal (Na(+) + K(+))-activated ATPase from rat intestinal mucosa has been studied and compared with their effects on L-phenylalanine and D-galactose transport by rings of rat intestine in vitro. A similar comparison between the sensitivities to ouabain of microsomal (Na(+) + K(+))-ATPase and of phenylalanine transport in the intestines of the mouse, guinea-pig and toad has been made.2. The rat intestinal enzyme is 50% inhibited by a concentration of 1 x 10(-4)M ouabain, 1 x 10(-5)M scillaren A and 4 x 10(-6)M scilliroside. At concentrations which almost completely inhibit the (Na(+) + K(+))-ATPase activity, these steroids have no effect on the transport of phenylalanine or galactose by the rat intestine. Only at concentrations of 1 x 10(-3)M are scillaren A and scilliroside able to reduce phenylalanine accumulation significantly, the same concentration of ouabain being effective only in the absence of external potassium ions. Digitoxin, 1 x 10(-4)M, a comparatively apolar glycoside, had no action on phenylalanine transport in the rat intestine.3. The effect of ouabain on the (Na(+) + K(+))-ATPase and phenylalanine transport system in the mouse intestine is completely analogous to its effect on these parameters in the rat.4. A half-maximal inhibition of guinea-pig intestinal (Na(+) + K(+))-ATPase by ouabain occurs at an inhibitor concentration of 2 x 10(-6)M, but phenylalanine transport by this tissue is only half-maximally reduced at a concentration of 3 x 10(-5)M. Similarly, in the rabbit intestine, there appears to be a difference of an order of magnitude between the sensitivities of the two parameters.5. In the toad, 50% inhibition of the enzymic activity is observed at a concentration of 3 x 10(-5)M ouabain, whereas a concentration of 8 x 10(-4)M is required to reduce phenylalanine accumulation by one half.6. These findings are consistent with the suggestion that an (Na(+) + K(+))-stimulated ATPase is not the only enzyme in the epithelial cells of the intestinal mucosa that is responsible for sodium extrusion (the mechanism for sodium extrusion being intimately coupled with the mechanism for active amino acid transport); therefore, a second, as yet unidentified, enzyme system must be postulated to account for bulk sodium flow through the intestine.