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 microM] 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 NG-monomethyl-L-arginine (L-NMMA) concentrations.
Mendes Ribeiro
A C
AC
University Laboratory of Physiology, Oxford, U.K. cribeiro@physiol.ox.ac.uk
Brunini
T M
TM
Yaqoob
M
M
Aronson
J K
JK
Mann
G E
GE
Ellory
J C
JC
D026923:Amino Acid Transport Systems, Basic; D001120:Arginine / Q000097:blood*; D001667:Binding, Competitive; D001692:Biological Transport / Q000187:drug effects; D001792:Blood Platelets / Q000378:metabolism*; D002352:Carrier Proteins / Q000097:blood*; D005973:Glutamine / Q000494:pharmacology; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood; D007700:Kinetics; D007930:Leucine / Q000494:pharmacology; D008565:Membrane Proteins / Q000097:blood*; D011188:Potassium / Q000494:pharmacology; D012964:Sodium / Q000494:pharmacology; D015854:Up-Regulation; D014511:Uremia / Q000097:blood*
D026923:Amino Acid Transport Systems, Basic; D002352:Carrier Proteins; D008565:Membrane Proteins; D005973:Glutamine; D001120:Arginine; D012964:Sodium; D007930:Leucine; D011188:Potassium