Role of nitric oxide in central synaptic transmission: effects on neurotransmitter release.
Nitric oxide (NO), an unstable radical formed via oxidative deamination of L-arginine by NO synthase, has the activity to evoke release of several neurotransmitters including acetylcholine, catecholamines and neuroactive amino acids. N-methyl-D-aspartate (NMDA) receptor stimulation also causes neurotransmitter release through NO formation, which is supported by the data extracellular hemoglobin completely abolishes the stimulatory effect of NMDA on neurotransmitter release. In addition, NO formed by NMDA receptor activation exhibits its stimulatory action on neurotransmitter release extracellularly. A product formed by the reaction of NO and superoxide, peroxynitrite, is also considered to be partly involved in NO-evoked neurotransmitter release. The removal of Ca2+ or Na+ significantly reduces the release of GABA evoked by an NO generator, S-nitroso-N-acetylpenicillamine (SNAP), and simultaneous withdrawal of these ions completely abolishes the SNAP-induced release of GABA. Either in the presence or absence of Ca2+, GABA transport inhibitors such as nipecotic acid dose-dependently suppress the SNAP-induced GABA release in the presence of Na+. These results indicate that NO-evoked neurotransmitter release is mediated by two distinct release systems, a Ca2(+)-dependent system and the reverse process of a Na(+)-dependent carrier-mediated transport system.
Kuriyama
K
K
Department of Pharmacology, Kyoto Prefectural University of Medicine, Japan.
Ohkuma
S
S
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009569:Nitric Oxide / Q000494:pharmacology*; D012964:Sodium / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018377:Neurotransmitter Agents; D009569:Nitric Oxide; D005680:gamma-Aminobutyric Acid; D012964:Sodium; D000109:Acetylcholine; D002118:Calcium