title: Modulation of the cationic amino acid transport system y+L by surface potential, ouabain and thrombin in human platelets: effects of uremia.
abstract: BACKGROUND
  Nitric oxide (NO), a key endogenous mediator involved in the maintenance of platelet function, is synthesized from the amino acid L-arginine. We have shown that L-arginine transport in platelets is rate-limiting for NO synthesis. A disturbance in the L-arginine-NO pathway in platelets was previously described in chronic renal failure (CRF) patients.
  
  
  METHODS
  Detailed kinetic studies were performed in platelets from controls (n = 60) and hemodialysis patients (n = 26).
  
  
  RESULTS
  The transport of L-arginine in platelets is mediated via system y+L, which is competitively inhibited by L-leucine in the presence of Na+ and by the irreversible inhibitor pCMB. In platelets, system y+L is markedly stimulated by an Na+/K+-ATPase inhibitor, ouabain, and by changes in surface potential, while it is downregulated by intraplatelet amino acid depletion (zero-trans) and by thrombin. In CRF patients, activation of L-arginine transport was limited to well-nourished patients compared to malnourished patients and controls, where it was reduced and did not differ significantly among the groups under zero-trans conditions.
  
  
  CONCLUSIONS
  Our results provide the first evidence that system y+L in platelets is modulated by zero-trans conditions, surface potential, thrombin and intraplatelet Na+ concentration. Our findings suggest that enhanced transport in CRF involves increased L-arginine exchange with intraplatelet neutral amino acids.
authors.affiliation: Departamento de Farmacologia e Psicobiologia, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Mariana
authors.initials: M
authors.lastname: Alves de Sá Siqueira
authors.forename: Marcela Anjos
authors.initials: MA
authors.lastname: Martins
authors.forename: Natália
authors.initials: N
authors.lastname: Rodrigues Pereira
authors.forename: Monique
authors.initials: M
authors.lastname: Bandeira Moss
authors.forename: Sérgio F F
authors.initials: SF
authors.lastname: Santos
authors.forename: Giovanni E
authors.initials: GE
authors.lastname: Mann
authors.forename: Antônio C
authors.initials: AC
authors.lastname: Mendes-Ribeiro
authors.forename: Tatiana M C
authors.initials: TM
authors.lastname: Brunini
mesh_terms: D000328:Adult; D027241:Amino Acid Transport System y+L / Q000378:metabolism*; D001120:Arginine / Q000493:pharmacokinetics; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D006490:Hemostatics / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007676:Kidney Failure, Chronic / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008564:Membrane Potentials; D009569:Nitric Oxide / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology*; D014316:Tritium; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014511:Uremia / Q000378:metabolism*
chemical_list: D027241:Amino Acid Transport System y+L; D004791:Enzyme Inhibitors; D006490:Hemostatics; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D014316:Tritium; D009569:Nitric Oxide; D010042:Ouabain; D001120:Arginine; D012964:Sodium; D013917:Thrombin; D005947:Glucose