CIS-INHIBITION AND TRANS-STIMULATION OF CATIONIC AMINO-ACID-TRANSPORT IN THE PERFUSED RAT PANCREAS

Transport of cationic amino acids in the isolated perfused rat pancreas was studied using dual-isotope dilution techniques. At 50-mu-M substrate concentration, unidirectional tracer uptakes for L-arginine (56 +/- 1%), L-lysine (49 +/- 2%), and L-ornithine (44 +/- 3%) were followed by rapid tracer efflux. In the presence of Na+, influx of L-arginine [Michaelis constant (K(m)) = 1.74 +/- 0.15 mM, maximum velocity (V(max)) = 1.97 +/- 0.07-mu-mol.min-1.g-1] and L-lysine (K(m) = 2.48 +/- 0.17 mM, V(max) = 2.42 +/- 0.08-mu-mol.min-1.g-1) was mediated by a common transport system, sensitive to cis-inhibition by L-ornithine, 2,4-L-diaminobutyric acid, D-lysine, and D-arginine. Substrates for system A [alpha-(methylamino)isobutyric acid] and an anionic carrier (L-aspartate) were poor cis-inhibitors of L-arginine entry. Removal of Na+ resulted in a 40% reduction in cationic amino acid influx. After cell loading (20 min), L-[H-3]-lysine cleared predominantly from a slowly exchanging pool with a rate constant of 5.97 +/- 0.67 min. An influx/efflux permeability ratio of 14.5 +/- 1.6 was determined, and efflux of L-lysine was trans-stimulated by vascular challenges with cationic or large neutral amino acids. The specificity, relative Na+ independence, and exchange properties of this saturable cationic amino acid transporter in the pancreatic epithelium resemble those reported for system y+ in cultured fibroblasts and hepatocytes.