Polyamines inhibit nitric oxide synthase in rat cerebellum

The polyamines spermine, spermidine and putrescine share some basic structural features with l-arginine, the substrate of nitric oxide (NO) synthase. The effects of the polyamines on neuronal NO synthase activity were studied in cytosolic preparations of rat cerebellum and cultured cerebellar granule neurons. Spermine, spermidine and putrescine all inhibited the conversion of [³H]l-arginine to [³H]l-citrulline by NO synthase, with the following rank order of potency: spermine > spermidine > putrescine. These inhibitory effects of the polyamines on [³H]l-citrulline formation were also observed in intact cultured cerebellar granule neurons upon stimulation of N-methyl-d-aspartate (NMDA) receptors. Evidence was obtained, however, that endogenous polyamines are not involved in regulation of NMDA-stimulated NO synthase activity. Thus, the observed inhibitory effects of exogenous polyamines might not reflect a physiological role in modulating NO generation in neurons.