MECHANISMS FOR FACILITATION OF NITRIC OXIDE-EVOKED [H-3]GABA RELEASE BY REMOVAL OF HYDROXYL RADICAL

We have investigated the mechanisms for enhancement of nitric oxide (N O)-evoked gamma-[H-3]aminobutyric acid ([H-3]GABA) release from mouse cerebrocortical neurons by hydroxyl radical ((OH)-O-.) scavengers. (OH )-O-. scavengers, such as N,N'-dimethylthiourea (DMTU), uric acid, and mannitol, dose-dependently facilitated NO-evoked [H-3]GABA release ev oked by NO liberated from S-nitroso-N-acetylpenicillamine. Ionomycin-e voked [H-3]GABA release, which was significantly inhibited by hemoglob in and an NO synthase, N-G-methyl-L-arginine, was also enhanced by DMT U. These results indicate that GABA release evoked by both endogenous and exogenous NO is facilitated by (OH)-O-. scavengers. These enhancin g actions of (OH)-O-. scavengers were completely abolished by Ca2+ rem oval from incubation buffer and by an L-type voltage-dependent Ca2+ ch annel (VDCC) inhibitor, nifedipine, whereas each (OH)-O-. scavenger sh owed no effects on [H-3]GABA release in the absence of NO. Inhibitors for P/Q- and N-type VDCCs had no effects on the enhancement. NO-induce d Ca-45(2+) influx was also dose-dependently enhanced by (OH)-O-. scav engers, although Ca-45(2+) influx was not altered by (OH)-O-. scavenge rs in the absence of NO. Nifedipine abolished this enhancement of the NO-induced Ca-45(2+) influx by (OH)-O-. scavengers. These results indi cate that the removal of (OH)-O-. by its scavengers facilitates the NO -evoked [H-3]GABA release dependent on Ca2+ and that this enhancement is due to the increase in Ca2+ influx via L-type VDCCs.