PMID- 12475743
OWN - NLM
STAT- MEDLINE
DCOM- 20030327
LR  - 20141120
IS  - 1931-857X (Print)
IS  - 1522-1466 (Linking)
VI  - 284
IP  - 4
DP  - 2003 Apr
TI  - Differential regulation of glomerular arginine transporters (CAT-1 and CAT-2) in 
      lipopolysaccharide-treated rats.
PG  - F788-95
AB  - The decrease in glomerular filtration rate (GFR) that is characteristic of sepsis 
      has been shown to result from inhibition of glomerular endothelial nitric oxide 
      synthase (eNOS) by nitric oxide (NO) generated from the inducible isoform of NOS 
      (iNOS). Although l-arginine is the sole precursor for NO biosynthesis, its 
      intracellular availability in glomeruli from septic animals has never been 
      investigated. Arginine uptake was measured in freshly harvested glomeruli from 
      the following experimental groups: 1) untreated rats; 2) rats pretreated with LPS 
      (4 mg/kg body wt, 4 h before experiments); 3) rats treated with LPS as above with 
      either l-N(6)-(1-iminoethyl)lysine hydrochloride (l-NIL), a selective iNOS 
      antagonist, or 7-nitroindazole, a selective neuronal NOS antagonist; and 4) rats 
      treated with l-NIL only. Both glomeular and mesangial arginine transport 
      characteristics were found compatible with a y(+) system. Arginine uptake was 
      augmented in glomeruli from LPS-treated rats. Treatment with l-NIL completely 
      abolished this effect whereas l-NIL alone had no effect. Similar results were 
      obtained when primary cultures of rat mesangial cells were preincubated with LPS 
      (10 microg/ml for 24 h) with or without l-NIL. Using RT-PCR, we found that in 
      vivo administration of LPS resulted in a significant increase in glomerular 
      cationic amino acid transporter-2 (CAT-2) mRNA expression whereas CAT-1 mRNA was 
      undetected. Northern blotting further confirmed a significant increase in 
      glomerular CAT-2 by LPS. In mesangial cells, the expression of both CAT-1 and 
      CAT-2 mRNA was augmented after incubation with LPS. In conclusion, in vivo 
      administration of LPS augments glomerular arginine transport through upregulation 
      of steady-state CAT-2 mRNA while downregulating CAT-1 mRNA. These results may 
      correspond to the changes in glomerular iNOS and eNOS activity in sepsis.
FAU - Schwartz, Doron
AU  - Schwartz D
AD  - Nephrology Department, The Tel Aviv Sourasky Medical Center, Tel Aviv 64239, 
      Israel. nmdri@netvision.net.il
FAU - Schwartz, Idit F
AU  - Schwartz IF
FAU - Gnessin, Ehud
AU  - Gnessin E
FAU - Wollman, Yoram
AU  - Wollman Y
FAU - Chernichovsky, Tamara
AU  - Chernichovsky T
FAU - Blum, Miriam
AU  - Blum M
FAU - Iaina, Adrian
AU  - Iaina A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20021210
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (Cationic Amino Acid Transporter 1)
RN  - 0 (Cationic Amino Acid Transporter 2)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (RNA, Messenger)
RN  - 94ZLA3W45F (Arginine)
RN  - 9NEZ333N27 (Sodium)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 1.14.13.39 (Nos2 protein, rat)
RN  - EC 1.14.13.39 (Nos3 protein, rat)
RN  - K3Z4F929H6 (Lysine)
SB  - IM
MH  - Animals
MH  - Arginine/pharmacokinetics
MH  - Cationic Amino Acid Transporter 1/genetics/*metabolism
MH  - Cationic Amino Acid Transporter 2/genetics/*metabolism
MH  - Cells, Cultured
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Gene Expression Regulation/drug effects
MH  - Glomerular Mesangium/cytology/drug effects/metabolism
MH  - In Vitro Techniques
MH  - Ion Transport/drug effects
MH  - Kidney Glomerulus/drug effects/*metabolism
MH  - *Lipopolysaccharides
MH  - Lysine/pharmacology
MH  - Male
MH  - Nitric Oxide Synthase/metabolism
MH  - Nitric Oxide Synthase Type II
MH  - Nitric Oxide Synthase Type III
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Sepsis/chemically induced/*metabolism
MH  - Sodium/pharmacology
EDAT- 2002/12/12 04:00
MHDA- 2003/03/28 05:00
CRDT- 2002/12/12 04:00
PHST- 2002/12/12 04:00 [pubmed]
PHST- 2003/03/28 05:00 [medline]
PHST- 2002/12/12 04:00 [entrez]
AID - 00221.2002 [pii]
AID - 10.1152/ajprenal.00221.2002 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2003 Apr;284(4):F788-95. doi: 
      10.1152/ajprenal.00221.2002. Epub 2002 Dec 10.