title: Transport of nitric oxide synthase inhibitors through cationic amino acid carriers in human erythrocytes.
abstract: The interaction of arginine analogues, which are known to inhibit nitric oxide synthase, with two cationic amino acid transporters of human erythrocytes (systems y+ and y+L) was studied. Arginine and relevant analogues [NG-monomethyl-L-arginine (L-NMMA); NG-monomethyl-D-arginine (D-NMMA) and NG-nitro-L-arginine (L-NOARG)] were found to inhibit labeled lysine influx into intact erythrocytes. As expected, the pattern of inhibition reflected the contribution of the two distinct transport systems. All analogues showed a higher affinity for system y+L than for system y+. The half-saturation (inhibition) constants estimated for systems y+ and y+L (+/- SEM) were (microM): L-arginine, 55.7 +/- 5.4 and 2.4 +/- 0.1; L-NMMA, 151 +/- 13 and 7.5 +/- 0.5; D-NMMA, 2660 +/- 404 and 269 +/- 25; L-NOARG, 9414 +/- 169 and 594 +/- 35. The transport properties of the analogues were investigated using an assay based on the trans-stimulation of lysine efflux. The addition of saturating concentrations of unlabeled analogues to the external medium stimulated efflux of labeled lysine through systems y+L and y+, showing that the analogues can enter the cell through these pathways.
authors.affiliation: Department of Physiology and Biophysics, Faculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: M I
authors.initials: MI
authors.lastname: Forray
authors.forename: S
authors.initials: S
authors.lastname: Angelo
authors.forename: C A
authors.initials: CA
authors.lastname: Boyd
authors.forename: R
authors.initials: R
authors.lastname: Devés
mesh_terms: D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002412:Cations; D004912:Erythrocytes / Q000378:metabolism*; D005033:Ethylmaleimide / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008239:Lysine / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine; D019323:omega-N-Methylarginine
chemical_list: D002412:Cations; D019335:Nitroarginine; D019323:omega-N-Methylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D008239:Lysine; D005033:Ethylmaleimide