Effects of nitric oxide donors on Ca2+-dependent [14C]GABA release from brain synaptosomes: the role of SH-groups.
Biochemistry (Mosc)
; 65(9): 1027-35, 2000 Sep.
Article
in En
| MEDLINE
| ID: mdl-11042494
ABSTRACT
Nitric oxide (NO) modulates processes of synaptic transmission at pre- and postsynaptic levels. In the present work we studied the mechanisms of action of NO on [gamma-14C]amino-n-butyric acid ([14C]GABA) release in rat cortical synaptosomes. NO donors--S-nitroso-L-cysteine and hydroxylamine (but not sodium nitroprusside)--inhibited the neurotransmitter efflux in a concentration range from 10 microM to 1 mM. Nitrosocysteine completely and selectively suppressed the Ca2+-dependent (vesicular) [14C]GABA release, while not affecting the Ca2+-independent component of the [14C]GABA transport. The influence of NO donors was not related to activation of guanylyl cyclase, since the membrane-permeable cGMP analog dibutyryl-cGMP did not mimic and the guanylyl cyclase inhibitor methylene blue did not change the NO effects. In contrast, the membrane-permeable SH-reagent N-ethylmaleimide (NEM) resembled the effects of NO donors on the Ca2+-dependent [14C]GABA release. The degree of inhibition of the release by nitrosocysteine, hydroxylamine, and NEM correlated with their ability to oxidize intra-synaptosomal SH-groups. These data suggest that synaptosomal sulfhydryl groups are the target for NO action at the presynaptic level. The NO-induced oxidation of thiols may be involved in physiological and, especially, pathological effects of nitric oxide in the central nervous system.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Synaptosomes
/
Brain
/
Carbon Isotopes
/
Calcium
/
Src Homology Domains
/
Nitric Oxide Donors
/
Cysteine
/
S-Nitrosothiols
/
Gamma-Aminobutyric Acid
Limits:
Animals
Language:
En
Journal:
Biochemistry (Mosc)
Year:
2000
Document type:
Article
Affiliation country:
Belarús