Identification of system y(+)L as the high-affinity transporter for L-arginine in human platelets: up-regulation of L-arginine influx in uraemia

Kinetic studies of L-arginine transport in human platelets have identified a high-affinity, low-capacity transport system [Michaelis-Menten constant ( K-m,) about 10 mu M] for cationic amino acids that also transports neutral amino acids with high affinity in the presence of Na+ but not Kf. These cha racteristics, together with our kinetic cis-inhibition studies, indicate th at saturable L-arginine transport in human platelets is mediated via the sy stem y(+)L and not the classic cationic transporter system y(+). We present here the first evidence that L-arginine transport via system y(+)L is incr eased twofold in platelets from patients with chronic renal failure. System y(+)L has been described in human erythrocytes, peripheral blood mononucle ar cells and placenta, and up-regulation of system y+L activity in human pl atelets could explain the paradox of increased nitric oxide (NO) production by uraemic platelets under conditions of decreased plasma L-arginine and e levated NG-monomethyl-L-arginine (L-NMMA) concentrations.