Incubation of rat astrocytes or C6 glioma cells with norepinephrine (N
E) suppresses bacterial endotoxin and cytokine-dependent induction of
calcium-independent nitric oxide synthase [Feinstein et al., J. Neuroc
hem., 60 (1993) 1945-1948]. We examined if NE also modified L-arginine
uptake. Overnight incubation in 10 mu M NE reduced the V-max for upta
ke by 30-40%, but did not decrease the apparent K-m for arginine. Shor
t incubation times (up to 90 min) with NE were without effect. The bet
a-adrenergic receptor agonist isoproterenol was as effective as NE in
reducing uptake, while the alpha-adrenergic receptor agonist phenyleph
rine produced a slight, but significant decrease. Arginine uptake was
similarly decreased by incubating cells with the cyclic AMP (cAMP) ana
log dibutyryl cAMP (dbcAMP). Both NE and dbcAMP potently blocked glial
cell proliferation, however the anti-mitogenic agent cytosine arabino
side had no effect on arginine uptake. These results support the conce
pt that glial cell arginine metabolism is regulated by endogenous neur
otransmitters such as NE. (C) 1997 Elsevier Science Ireland Ltd.