GLUTAMATE-INDUCED RELEASE OF THE NITRIC-OXIDE PRECURSOR, ARGININE, FROM GLIAL-CELLS

Arginine, the nitric oxide precursor, is predominantly localized in gl ial cells, whereas the constitutive nitric oxide synthase is mainly fo und in neurons. Therefore? a transfer of arginine from glial cells to neurons is needed to replenish the neuronal precursor pool. This is fu rther supported by the finding that arginine is released upon selectiv e pathway stimulation both in vitro and in vivo. We investigated the m echanism underlying this glial-neuronal interaction by analysing the e ffect of glutamate receptor agonists on the extracellular [H-3]arginin e level in cerebellar and cortical slices and in cultures of either co rtical astroglial cells or neurons. We present data indicating that ar ginine is released from cerebellar and cortical slices and astroglial cell cultures upon activation of ionotropic non-NMDA glutamate recepto rs. Glutamate had no effect on the extracellular [H-3]arginine level i n neuronal cultures. Moreover, the effect of glutamate in cerebellar s lices was tetrodotoxin-insensitive, and the calcium ionophore A23187 e voked the release of [H-3]arginine from astroglial cell cultures. Thus , nitric oxide synthesis and nitric oxide transmission may be based on the glial-neuronal transfer of arginine which is induced by activatio n of excitatory amino acid receptors on glial cells.