Experimental cystinuria: the cycloleucine model. I. Amino acid interactions in renal and intestinal epithelia.
The injection of cycloleucine (1-aminocyclopentanecarboxylic acid (ACPC) into rats produces a hyperexcretion of dibasic amino acids and cystine, an aberration resembling cystinuria. This may constitute a model of experimental cystinuria, and the transport of amino acids involved in this disease was studied with the techniques of everted intestinal sacs (in vitro) and microinjections into renal tubules (in vivo). In verted sacs from normal rats, there was a decrease in transfer and in accumulation of L-cystine (0.03 mM) and L-valine (0.065 mM) when ACPC was on the mucosal (luminal) side. Dibasic amino acids such as L-arginine and L-lysine caused a similar inhibition of the transport of L-cystine. However, when ACPC was on the serosal (antiluminal) side, a lesser effect was noted while arginine and lysine had no effect. Intestinal sacs from treated rats (ACPC, 300 mg/kg X 3 days) transferred and accumulated as much L-cystine as those from control rats. The interaction between cycloleucine and L-cystine was competitive at the luminal and non-competitive at the antiluminal side of the intestine. Cycloleucine inhibited L-lysine transport in a non-competitive fashion at either side of the intestine. L-Lysine also interacted in a non-competitive fashion with L-cystine transport at the luminal membrane. In proximal convoluted tubules, the presence of L-arginine or ACPC caused a decrease in the transport of L-cystine and L-lysine. L-Valine exerted no effect. Furthermore, L-lysine and ACPC did not impair the reabsorption of L-valine significantly. These results suggest a functional heterogeneity between luminal and antiluminal membranes of renal and intestinal epitehlia and the existence, at both membranes, of different transport sites for cystine and dibasic amino acids.
D000596:Amino Acids / Q000378:metabolism* / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D003515:Cycloleucine / Q000494:pharmacology*; D003553:Cystine / Q000378:metabolism; D003555:Cystinuria / Q000139:chemically induced / Q000378:metabolism*; D003864:Depression, Chemical; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005260:Female; D007413:Intestinal Mucosa / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism; D007700:Kinetics; D051381:Rats
D000596:Amino Acids; D003515:Cycloleucine; D003553:Cystine