Elsevier

Neuroscience Letters

Volume 190, Issue 3, 12 May 1995, Pages 195-198
Neuroscience Letters

Complex involvement of nitric oxide and cGMP at N-methyl-d-aspartic acid receptors regulating γ-[3H]aminobutyric acid release from striatal slices

https://doi.org/10.1016/0304-3940(95)11538-8Get rights and content

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 γ-[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.

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    Supported by the National Health and Medical Research Council (Australia) of which P.M.B. is a Principal Research Fellow. M.M. acknowledges support from the Royal Danish School of Pharmacy.

    1

    Present address: Royal Danish School of Pharmacy, 2 Universitetsparken, DK-2100 Copenhagen, Denmark.

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