Regulation of neurotransmitter release by endogenous nitric oxide in striatal slices

Taleen Hanania, Kenneth M. Johnson

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


This study sought to determine the potential role of nitric oxide (NO) in N-methyl-d-aspartate (NMDA)-stimulated efflux of [14C] γ-aminobutyric acid (GABA) and [3H]acetylcholine from striatal slices in vitro. In Mg2+-free buffer, NMDA-stimulated [14C]GABA and [3H]acetylcholine release were inhibited by the guanylate cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), and, to a lesser extent, by the nitric oxide synthase inhibitor, nitroarginine (N-Arg). Since reversal of catecholamine transporters previously has been implicated in the mechanism underlying NO-induced catecholamine release, we used the GABA transport inhibitor, 1-(2-(((diphenylmethylene)imino)oxy)ethyl)-1,2,5,6-tetrahydro-3-pyridine-carboxylic acid hydrochloride (NNC-711), to address the role of GABA transport in NArg-sensitive NMDA-induced release. NNC-711 inhibited NMDA-stimulated [14C]GABA efflux by 50%, confirming our previous report that NMDA-stimulated GABA release is partially dependent on reversal of the transporter. The effect of N-Arg in the presence of NNC-711 was similar to its effect in the absence of the transport inhibitor, suggesting that reversal of the transporter is not involved in the NO component of NMDA-stimulated [14C]GABA release. These data suggest that glutamatergic transmission through striatal NMDA receptors is partially mediated through activation of the NO/guanylate cyclase pathway and that this mechanism may contribute to the tetrodotoxin sensitivity of NMDA-induced release of GABA and acetylcholine in the striatum. Copyright (C) 1998 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)111-117
Number of pages7
JournalEuropean Journal of Pharmacology
Issue number2-3
StatePublished - Oct 23 1998
Externally publishedYes


  • Acetylcholine release
  • GABA (γ-aminobutyric acid) release
  • NMDA receptor
  • Nitric oxide (NO)
  • Striatum

ASJC Scopus subject areas

  • Pharmacology


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