Effect of nitric oxide donor SNAP on GABA release from rat brain nerve terminals

• Published in: Ukrainian biochemical journal 2016-09, Vol.88 (5), p.82-89
• Main Author: Tarasenko, A S
• Format: Article
• Language: English
• Subjects: 4-Aminopyridine - pharmacology; Aniline Compounds - chemistry; Animals; Calcium - metabolism; Cerebral Cortex - chemistry; Cerebral Cortex - metabolism; Dithiothreitol - pharmacology; Fluorescent Dyes - chemistry; GABA release; gamma-Aminobutyric Acid - secretion; Hippocampus - chemistry; Hippocampus - metabolism; Kinetics; Male; Nipecotic Acids - pharmacology; nitric oxide; Nitric Oxide - chemistry; Nitric Oxide - pharmacology; Presynaptic Terminals - drug effects; Presynaptic Terminals - metabolism; Rats; Rats, Wistar; S-Nitroso-N-Acetylpenicillamine - chemistry; S-Nitroso-N-Acetylpenicillamine - pharmacology; Synaptosomes - drug effects; Synaptosomes - metabolism; vesicular and cytoplasmic pool; Xanthenes - chemistry
• ISSN: 2409-4943; 2413-5003
• DOI: 10.15407/ubj88.05.082

In this work we investigated the effect of nanomolar concentrations of nitric oxide on the release of gamma-aminobutyric acid (GABA) from rat brain nerve terminals using a radioisotope method with [3H]GABA and a spectrofluorimetric method with Ca2+-sensitive probe Fluo-4 AM. It was shown that in the presen­ce of dithiothreitol (DTT), nitric oxide donor SNAP at concentration, in which it produces NO in the nanomolar range, caused Ca2+-independent [3H]GABA release from nerve terminals. The applications of 4-aminopyridine (4-AP) and nipecotic acid (NA), as the inducers of GABA release from vesicular and cytoplasmic pools, showed that the maximum of SNAP/+DTT-induced [3H]GABA release was registered at 10th min of incubation and coincided in time with significant increase (almost double) in NA-induced [3H]GABA release. At this time point, 4-AP-induced release of [3H]GABA was drastically reduced. At the 15th min of incubation of nerve terminals with SNAP/+DTT, the opposite picture was observed: the decrease in NA- and increase in 4-AP-induced [3H]GABA release. Thus, nitric oxide in the form of S-nitrosothiols at nanomolar concentrations causes Ca2+-independent GABA leakage from synaptic vesicles into cytosol with subsequent release from nerve terminals. The reuptake of the neurotransmitter and its re-accumulation in synaptic vesicles occur later.