title: Cis-inhibition and trans-stimulation of cationic amino acid transport in the perfused rat pancreas.
abstract: Transport of cationic amino acids in the isolated perfused rat pancreas was studied using dual-isotope dilution techniques. At 50 microM 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 (Km) = 1.74 +/- 0.15 mM, maximum velocity (Vmax) = 1.97 +/- 0.07 mumol.min-1.g-1] and L-lysine (Km = 2.48 +/- 0.17 mM, Vmax = 2.42 +/- 0.08 mumol.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-[3H]-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.
authors.affiliation: Biomedical Sciences Division, King's College London, United Kingdom.
authors.forename: J H
authors.initials: JH
authors.lastname: Sweiry
authors.forename: M
authors.initials: M
authors.lastname: Muñoz
authors.forename: G E
authors.initials: GE
authors.lastname: Mann
mesh_terms: D019297:2,4-Dinitrophenol; D000596:Amino Acids / Q000494:pharmacology; D000599:Amino Acids, Diamino / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D004140:Dinitrophenols / Q000494:pharmacology; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008239:Lysine / Q000378:metabolism; D008297:Male; D008353:Mannitol / Q000378:metabolism; D009952:Ornithine / Q000378:metabolism; D010101:Oxygen Consumption; D010179:Pancreas / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D000596:Amino Acids; D000599:Amino Acids, Diamino; D004140:Dinitrophenols; D008353:Mannitol; D001120:Arginine; D009952:Ornithine; D008239:Lysine; D019297:2,4-Dinitrophenol