NOREPINEPHRINE SUPPRESSES L-ARGININE UPTAKE IN RAT GLIAL-CELLS

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.