Mechanisms for Facilitation of Nitric Oxide-Evoked [3H]GABA Release by Removal of Hydroxyl Radical |
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Authors: | Seitaro Ohkuma Masashi Katsura †Yasushi Hibino Atsuo Hara ‡Kenji Shirotani †Emiko Ishikawa †Kinya Kuriyama |
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Institution: | Departments of Pharmacology and; Urology, Kawasaki Medical School, Kurashiki;and; Department of Pharmacology, Kyoto Prefectural University of Medicine, Kyoto, Japan |
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Abstract: | Abstract: We have investigated the mechanisms for enhancement of nitric oxide (NO)-evoked γ-3H]aminobutyric acid (3H]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 3H]GABA release evoked by NO liberated from S-nitroso-N-acetylpenicillamine. Ionomycin-evoked 3H]GABA release, which was significantly inhibited by hemoglobin and an NO synthase, NG-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 Ca2+ removal from incubation buffer and by an l -type voltage-dependent Ca2+ channel (VDCC) inhibitor, nifedipine, whereas each ?OH scavenger showed no effects on 3H]GABA release in the absence of NO. Inhibitors for P/Q- and N-type VDCCs had no effects on the enhancement. NO-induced 45Ca2+ influx was also dose-dependently enhanced by ?OH scavengers, although 45Ca2+ influx was not altered by ?OH scavengers in the absence of NO. Nifedipine abolished this enhancement of the NO-induced 45Ca2+ influx by ?OH scavengers. These results indicate that the removal of ?OH by its scavengers facilitates the NO-evoked 3H]GABA release dependent on Ca2+ and that this enhancement is due to the increase in Ca2+ influx via L-type VDCCs. |
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Keywords: | Nitric oxide Hydroxyl radical GABA release Calcium influx Voltage-dependent calcium channel Cerebral cortical neurons |
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