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Mechanisms for Facilitation of Nitric Oxide‐Evoked [ 3 H]GABA Release by Removal of Hydroxyl Radical
Author(s) -
Ohkuma Seitaro,
Katsura Masashi,
Hibino Yasushi,
Hara Atsuo,
Shirotani Kenji,
Ishikawa Emiko,
Kuriyama Kinya
Publication year - 1998
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1998.71041501.x
Subject(s) - chemistry , nitric oxide , nifedipine , biophysics , ionomycin , hydroxyl radical , scavenger , gamma aminobutyric acid , calcium , biochemistry , pharmacology , radical , intracellular , receptor , medicine , organic chemistry , biology
We have investigated the mechanisms for enhancement of nitric oxide (NO)‐evoked γ‐[ 3 H]aminobutyric acid ([ 3 H]GABA) release from mouse cerebro‐cortical neurons by hydroxyl radical ( • OH) scavengers. • OH scavengers, such as N,N′ ‐dimethylthiourea (DMTU), uric acid, and mannitol, dose‐dependently facilitated NO‐evoked [ 3 H]GABA release evoked by NO liberated from S ‐nitroso‐ N ‐acetylpenicillamine. Ionomycin‐evoked [ 3 H]GABA release, which was significantly inhibited by hemoglobin and an NO synthase, N G ‐methyl‐ l ‐arginine, was also enhanced by DMTU. These results indicate that GABA release evoked by both endogenous and exogenous NO is facilitated by • OH scavengers. These enhancing actions of • OH scavengers were completely abolished by Ca 2+ removal from incubation buffer and by an l ‐type voltage‐dependent Ca 2+ channel (VDCC) inhibitor, nifedipine, whereas each • OH scavenger showed no effects on [ 3 H]GABA release in the absence of NO. Inhibitors for P/Q‐ and N‐type VDCCs had no effects on the enhancement. NO‐induced 45 Ca 2+ influx was also dose‐dependently enhanced by • OH scavengers, although 45 Ca 2+ influx was not altered by • OH scavengers in the absence of NO. Nifedipine abolished this enhancement of the NO‐induced 45 Ca 2+ influx by • OH scavengers. These results indicate that the removal of • OH by its scavengers facilitates the NO‐evoked [ 3 H]GABA release dependent on Ca 2+ and that this enhancement is due to the increase in Ca 2+ influx via L‐type VDCCs.