title: Complex involvement of nitric oxide and cGMP at N-methyl-D-aspartic acid receptors regulating gamma-[3H]aminobutyric acid release from striatal slices.
abstract: Whilst the depolarization of postsynaptic N-methyl-D-aspartic acid (NMDA) receptors leads to an influx of Ca2+ and subsequent synthesis of nitric oxide (NO), we examined roles for NO at striatal NMDA receptors regulating transmitter release. In superfused rat striatal slices, NMDA-evoked release of gamma-[3H]aminobutyric acid ([3H]GABA) was investigated in the presence of nitrergic drugs. NMDA-induced release of [3H]GABA was attenuated by D-2-aminophosphonopentanoate, tetrodotoxin and omission of Ca2+. L-Arginine enhanced NMDA-evoked release of [3H]GABA, but exogenous NO donors were ineffective. Inhibitors of NO synthase (NG-nitro- and NG-amino-L-arginine) and guanylate cyclase (LY83583) elevated release. Since NMDA-evoked release of [3H]GABA was partially tetrodotoxin-sensitive, nitrergic-linked NMDA receptors regulating the release are both pre- and extrasynaptic. Thus not only does NO arise from multiple sites, and involve NMDA receptors with their redox site insensitive to exogenous NO donors, but the NMDA receptors are under the influence of nitrergic and cGMP-linked negative feedback mechanisms.
authors.affiliation: Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Møller
authors.forename: N M
authors.initials: NM
authors.lastname: Jones
authors.forename: P M
authors.initials: PM
authors.lastname: Beart
mesh_terms: D000613:Aminobutyrates / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D006152:Cyclic GMP / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D000613:Aminobutyrates; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; D005680:gamma-Aminobutyric Acid; D001120:Arginine; D006152:Cyclic GMP