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

Abstract.

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 µM] for cationic amino acids that also transports neutral amino acids with high affinity in the presence of Na⁺ but not K⁺. These characteristics, together with our kinetic cis-inhibition studies, indicate that saturable l-arginine transport in human platelets is mediated via the system 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 increased twofold in platelets from patients with chronic renal failure. System y⁺L has been described in human erythrocytes, peripheral blood mononuclear cells and placenta, and up-regulation of system y⁺L activity in human platelets could explain the paradox of increased nitric oxide (NO) production by uraemic platelets under conditions of decreased plasma l-arginine and elevated N ^G-monomethyl-l-arginine (L-NMMA) concentrations.