Nitric oxide inhibition of the depolarization-evoked glutamate release from synaptosomes of rat cerebellum

Abstract

Effects of nitric oxide (NO) on release of amino acid transmitter were investigated by superfusion of synaptosomes prepared from rat cerebellum. After constant basal levels of amino acid release were obtained, exposure to a depolarizing concentration of KC1 (30 mM) evoked 4.05-, 2.18- and 3.00-fold increases in release of glutamic acid (Glu), aspartic acid (Asp) and γ-aminobutyric acid (GABA) from synaptosomes. The perfusion with NO-donors inhibited the evoked increases in release of Glu and Asp in a concentration-dependent manner, but not that in GABA release. A membrane-permeable analog of cyclic GMP, but not that of cyclic AMP, caused a similar reduction in the evoked release. The concentration of nitroprusside to increase cyclic GMP levels corresponded to that of nitroprusside to reduce the evoked release. These data suggest that NO may directly act upon the nerve terminals to inhibit release of excitatory amino acid transmitters.