NITRIC-OXIDE DIFFERENTIALLY AFFECTS THE EXOCYTOTIC AND THE CARRIER-MEDIATED RELEASE OF [H-3]GAMMA-AMINOBUTYRIC ACID IN RAT HIPPOCAMPAL SYNAPTOSOMES

We studied the effects of nitric oxide (NO) on the Ca2+-dependent KCl- evoked release of gamma-aminobutyric acid (GABA) by rat hippocampal sy naptosomes, measured in the presence of xy)ethyl)-1,2,5,6-tetrahydro-3 -pyridine-carboxylic acid (NNC-711), which blocks the GABA carrier. Un der these conditions, the NO donor, hydroxylamine, up to 1 mM, inhibit ed the Ca2+-dependent exocytotic GABA release, but did not affect the basal release. However, in the absence of NNC-711, hydroxylamine conce ntrations higher than 30 mu M caused a two-fold increase in the basal release of GABA, and the KCl-evoked release of GABA was higher than in the presence of NNC-711 because both exocytotic and carrier-mediated release occur. Thus, it is expected that when both release mechanisms are operative, NO inhibits the exocytotic release and stimulates the c arrier-mediated release, and the overall effect is an increased libera tion of the neurotransmitter from the nerve terminals. (C) 1998 Elsevi er Science B.V.