Abstract:
:The current study was designed to investigate the importance of cationic amino acid transporters (CATs) for the L-arginine supply to nitric oxide (NO) synthases in mouse J774A.1 macrophages and human EA.hy926 endothelial cells. CAT-1 was expressed in both cell types, whereas CAT-2B was only expressed in activated macrophages. Apparent K(M) values for transport of L-arginine in both cell types was consistent with the expression of the system y(+) carriers CAT-1 (and CAT-2B in macrophages). In addition, L-arginine transport was Na(+) independent and sensitive to trans-stimulation. A 2-h preincubation of activated macrophages in 2 mM L-lysine (which is exchanged for L-arginine by the CATs) reduced the intracellular L-arginine concentration from 2 mM to 160 microM. At the same time, nitric-oxide synthase (NOS) II activity was completely abolished. NOS II activity could be restored with extracellular L-arginine. No difference in NO production was seen between macrophages preincubated in L-arginine-containing buffer and incubated either with or without L-arginine during the 2-min NO assay. Incubation of endothelial cells in 2 mM L-lysine for up to 24 h decreased the intracellular L-arginine concentration from 3.5 mM to about 600 microM but did not reduce the NOS III activity. Our results suggest that both activated macrophages and endothelial cells have an L-arginine pool that is not freely exchangeable with the extracellular space. This pool seems to be accessible to NOS III in endothelial cells but not to NOS II in macrophages.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Closs EI,Scheld JS,Sharafi M,Förstermann Ukeywords:
subject
Has Abstractpub_date
2000-01-01 00:00:00pages
68-74issue
1eissn
0026-895Xissn
1521-0111journal_volume
57pub_type
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