Characterization of cationic amino acid transport systems in rat erythrocytes: lack of effect of uraemia on L-arginine influx.
1. Chronic renal failure (CRF) is associated with the abnormal regulation of nitric oxide (NO) synthesis at the systemic level. The transport of L-arginine, upregulated in blood cells from uraemic patients, modulates NO synthesis in this pathological condition. The model of partial nephrectomy in rats is widely accepted as a valid model of uraemia. Because there are no reports of L-arginine transport in blood cells from uraemic rats, the aim of the present study was to investigate L-arginine transport in red blood cells (RBCs) from these rats. 2. The kinetics of L-arginine transport in RBC and plasma and the amino acid profiles of RBC were investigated in control, sham-operated and subtotally nephrectomized rats. 3. L-Arginine transport was mediated via the cationic amino acid transport system y+ and a transport system with kinetics resembling the human system y+L. In control RBC, the apparent Ki for L-leucine inhibition of L-arginine transport via system y+L was 0.16 +/- 0.02 and 4.8 +/- 2 mmol/L in the presence of Li+ and Na+, respectively. 4. The Vmax values for L-arginine transport via system y+L and system y+ were similar in RBC from control sham-operated and uraemic rats. Moreover, L-arginine concentrations in plasma and RBC were not affected by uraemia. 5. The findings of the present study provide the first evidence that L-arginine transport in rat erythrocytes is mediated by two distinct cationic transport systems with characteristics of systems y+ and y+L, which accept neutral amino acids only in the presence of Li+. In contrast with previous studies in uraemic patients, plasma levels and maximal transport rates of L-arginine were not altered in this rat model of CRF.
Brunini
T M C
TM
Departamento de Farmacologia e Psicobiologia, Instituto de Biologia, Universidade do Estado do Rio de Janeiro, Brazil.
Yaqoob
M M
MM
Roberts
N B
NB
Ellory
J C
JC
Moss
M B
MB
Siqueira
M A S
MA
Mann
G E
GE
Mendes Ribeiro
A C
AC
D027182:Amino Acid Transport System y+ / Q000037:antagonists & inhibitors / Q000378:metabolism*; D027241:Amino Acid Transport System y+L / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D002956:Citrulline / Q000097:blood; D004195:Disease Models, Animal; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D007930:Leucine / Q000097:blood / Q000494:pharmacology; D008239:Lysine / Q000097:blood / Q000494:pharmacology; D008297:Male; D009392:Nephrectomy; D009952:Ornithine / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D014511:Uremia / Q000097:blood / Q000378:metabolism*
D027182:Amino Acid Transport System y+; D027241:Amino Acid Transport System y+L; D002956:Citrulline; D001120:Arginine; D009952:Ornithine; D007930:Leucine; D008239:Lysine