DEXAMETHASONE UP-REGULATES A CONSTITUTIVE NITRIC-OXIDE SYNTHASE IN CEREBELLAR ASTROCYTES BUT NOT IN GRANULE CELLS IN CULTURE

Treatment of rat cerebellar astrocyte-enriched primary cultures with d examethasone enhances the nitric oxide-dependent cyclic GMP formation induced by noradrenaline in a time(>6 h) and concentration-dependent m anner (half-maximal effect at 1 nM). Stimulation of cyclic GMP formati on by the calcium ionophore A23187 is similarly enhanced. In contrast, cyclic GMP accumulation in cells treated with lipopolysaccharide is i nhibited by dexamethasone. The potentiating effect of dexamethasone is prevented by the protein synthesis inhibitor cycloheximide and is not due to increased soluble guanylate cyclase activity. Agonist stimulat ion of [H-3] arginine to [H-3]citrulline conversion is enhanced by dex amethasone in astrocytes but not in cerebellar granule cells. These re sults indicate that glucocorticoids may up-regulate astroglial calcium -dependent nitric oxide synthase while preventing expression of induci ble nitric oxide synthase and are the first report of a differential l ong-term regulation of the expression of neuronal and astroglial const itutive nitric oxide synthase activities.