Arginine transport is augmented, through modulation of cationic amino acid transporter-1, in obstructive uropathy in rats.
BACKGROUND
The decrease in glomerular filtration rate (GFR), which is characteristic of obstructive uropathy, was suggested to be associated with attenuated nitric oxide (NO) generation. Since availability of L-arginine, the sole precursor for NO, governs NO synthesis, we aimed to determine the role of glomerular arginine transport in rats subjected to 24 h of bilateral ureteral ligation (BUO).


METHODS
Glomerular arginine transport was measured by uptake of radiolabeled arginine ([(3)H]-L-arginine), cationic amino acid transporters (CAT)-1 and -2 and arginases I and II mRNA expression were determined using reverse transcription-polymerase chain reaction. CAT-1, arginase I, and arginase II protein contents were evaluated by Western blotting.


RESULTS
L-Arginine transport by freshly harvested glomeruli from BUO rats was significantly augmented than in controls. The aforementioned findings were associated with a significant increase in glomerular CAT-1 mRNA expression, while CAT-2 mRNA was unchanged. Western blotting demonstrated a significant increase in CAT-1 abundance in BUO. Expression of both glomerular arginase I and II mRNA and protein content were significantly elevated in BUO.


CONCLUSIONS
BUO induces an increase in glomerular arginine transport via upregulation of CAT-1, probably due to increase in arginine utilization by a non-NO pathway.
Nephrology Department, Tel Aviv Sourasky Medical Center, Tel Aviv University, Sackler School of Medicine, Tel Aviv, Israel. nmdri@netvision.net.il
Idit F
IF
Schwartz
Aharon
A
Davidovitz
Tamara
T
Chernichovski
Nomi
N
Levin-Iaina
Hanan
H
Guzner-Gur
Yoram
Y
Levo
Doron
D
Schwartz
D000818:Animals; D001119:Arginase / Q000032:analysis / Q000235:genetics; D001120:Arginine / Q000378:metabolism*; D001692:Biological Transport; D027201:Cationic Amino Acid Transporter 1 / Q000032:analysis* / Q000235:genetics; D027202:Cationic Amino Acid Transporter 2 / Q000032:analysis / Q000235:genetics; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D007674:Kidney Diseases / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats
D027201:Cationic Amino Acid Transporter 1; D027202:Cationic Amino Acid Transporter 2; D012333:RNA, Messenger; D001120:Arginine; C113162:Arg2 protein, rat; D001119:Arginase