Nitric oxide differentially affects the exocytotic and the carrier-mediated release of [3H] 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 synaptosomes, measured in the presence of 1-(2-(((diphenyl-methylene)amino)oxy)ethyl)-1,2,5, 6-tetrahydro-3-pyridine-carboxylic acid (NNC-711), which blocks the GABA carrier. Under these conditions, the NO donor, hydroxylamine, up to 1 mM, inhibited the Ca2+-dependent exocytotic GABA release, but did not affect the basal release. However, in the absence of NNC-711, hydroxylamine concentrations higher than 30 microM 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 carrier-mediated release, and the overall effect is an increased liberation of the neurotransmitter from the nerve terminals.
Sequeira
S M
SM
Center for Neuroscience of Coimbra, Department of Zoology and Faculty of Medicine, University of Coimbra, 3000 Coimbra, Portugal.
Duarte
C B
CB
Carvalho
A P
AP
Carvalho
C M
CM
D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D005089:Exocytosis / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000494:pharmacology*; D051381:Rats; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D002352:Carrier Proteins; D009569:Nitric Oxide; D005680:gamma-Aminobutyric Acid