Norepinephrine induces a rapid and concentration-dependent rise (EC50 = 1.21 +/- 0.33-mu-M) in cyclic GMP levels in astrocyte-enriched cultures from rat brain. The response is partially mediated by alpha-1-adrenoceptors since a marked inhibition is observed in the presence of prazosin while the beta-antagonist propranolol shows a smaller effect and the alpha-2-antagonist yohimbine is ineffective. L-N(G)-methylarginine, an inhibitor of nitric oxide synthesis from L-arginine, blocks the norepinephrine-induced cyclic GMP accumulation. This effect is reversed by L-arginine.