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Vol. 57, Issue 1, 68-74, January 2000
Department of Pharmacology, Johannes Gutenberg University, Mainz,
Germany
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 KM 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 µM. 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 µM 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.
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