Interactions between neutral and dibasic amino acids for uptake by the rat intestine.

Abstract

Kinetic studies on the interaction between neutral and dibasic amino acids for absorption by the rat intestine have been performed. l‐Arginine uptake is stimulated by l‐citrulline, the kinetics formally revealing “uncompetitive” stimulation. l‐Isoleucine inhibits l‐arginine uptake “uncompetitively”. In the case of l‐methionine and l‐leucine, stimulation occurs at low concentrations of the neutral amino acid, but inhibition occurs at higher concentrations. The double reciprocal plots bisect in the first quadrant. Arginine inhibits the uptake of both methionine and citrulline, the kinetics being consistent with partially competitive inhibition. These kinetic situations were observed by means of steady‐state observations, but appear to be paralleled when initial velocities are determined.Efflux of arginine from a preloaded tissue is stimulated by external neutral amino acids, though not to such an extent as by arginine itself. Similarly, the efflux of neutral amino acids is stimulated to a lesser extent by external arginine than by the same or different external neutral amino acids.Intracellular methionine inhibits arginine efflux, and the efflux coefficient for arginine, determined from isotopic exchange experiments, is depressed by methionine. These results suggest that the stimulation of net arginine uptake by methionine may be explained in terms of an inhibition of arginine efflux. Intracellular citrulline and isoleucine have no effect on arginine efflux, however.Preloading with neutral amino acids produces the same effect on arginine uptake as the presence of these amino acids in the incubation medium. Although preloading with unlabelled arginine has no influence on the subsequent uptake of labelled arginine, it does tend to neutralise the isoleucine‐inhibition or the citrulline‐stimulation of arginine uptake. Methionine stimulation is, on the other hand, not affected by this preloading. This and other results suggest an intracellular locus of action of citrulline and isoleucine. Indeed these two amino acids seem to act in a similar manner but with an opposite effect on arginine uptake.