NOREPINEPHRINE INCREASES CYCLIC-GMP LEVELS IN CEREBELLAR CELLS FROM NEURONAL NITRIC-OXIDE SYNTHASE KNOCKOUT MICE

Cyclic GMP is an important intracellular messenger in the nervous syst em that may mediate cellular forms of neuronal plasticity. Previous st udies show that most neurotransmitters stimulate cyclic GMP levels by the activation of nitric oxide synthase (NOS). In this study, we repor t that in primary cell cultures from the cerebellum of neuronal NOS kn ockout mice, norepinephrine stimulates an increase in cyclic GMP conte nt. This increase is seen in both granule cell and astrocyte cultures and is not blocked by inhibitors of NOS or by inhibition of soluble gu anylyl cyclase. These results suggest a novel pathway by which norepin ephrine enhances cyclic GMP levels in the nervous system.