Competitive inhibition of dibasic amino acid transport in rat kidney.

It has long been postulated that the dibasic amino acids, lysine, arginine, ornithine, and cystine, share a common renal tubular transport mechanism. This hypothesis has developed from two separate but related lines of evidence. The canine and human renal clearance studies of Pitts, Webber, and Brown (1, 2), Wright et al. (3), Beyer et al. (4), Kamin and Handler (5), and Robson and Rose (6) all showed that infusion of one dibasic amino acid selectively increased urinary excretion and clearance of other dibasic amino acids. Several investigations of urinary amino acid excretion in human cystinuria have indicated that renal tubular reabsorption of these four dibasic amino acids is defective in this disease (7-10). Although the above noted renal clearance studies have convincingly demonstrated mutual interference between members of this group of structurally related compounds, the techniques used prohibited distinction between noncompetitive inhibition of transport due to toxic or osmotic effects of the infused amino acids and true competitive inhibition resulting from mutual affinity for a common transport site. For this reason, it seemed pertinent to investigate renal transport of this group of dibasic amino acids by using kidney tissue in vitro, where experimental conditions could be more precisely controlled than in intact animals or human subjects. The present report indicates that r&sine, n-arginine, and L-cystine are concentrated against chemical gradients by rat kidney cortex slices. Furthermore, the results offer evidence for competitive inhibition of transport between n-arginine, n-lysine, and n-ornithine by a mechanism (or mechanisms) that is not shared by n-cystine.