Norepinephrine suppresses L-arginine uptake in rat glial cells

Incubation of rat astrocytes or C6 glioma cells with norepinephrine (NE) suppresses bacterial endotoxin and cytokine-dependent induction of calcium-independent nitric oxide synthase (Feinstein et al., J. Neurochem., 60 (1993) 1945-1948]. We examined if NE also modified L-arginine uptake. Overnight incubation in 10 microM NE reduced the Vmax for uptake by 30-40%, but did not decrease the apparent Km for arginine. Short incubation times (up to 90 min) with NE were without effect. The beta-adrenergic receptor agonist isoproterenol was as effective as NE in reducing uptake, while the alpha-adrenergic receptor agonist phenylephrine produced a slight, but significant decrease. Arginine uptake was similarly decreased by incubating cells with the cyclic AMP (cAMP) analog dibutyryl cAMP (dbcAMP). Both NE and dbcAMP potently blocked glial cell proliferation, however the anti-mitogenic agent cytosine arabinoside had no effect on arginine uptake. These results support the concept that glial cell arginine metabolism is regulated by endogenous neotransmitters such as NE.