Regulation of neurotransmitter release by endogenous nitric oxide in striatal slices.
This study sought to determine the potential role of nitric oxide (NO) in N-methyl-D-aspartate (NMDA)-stimulated efflux of [14C] gamma-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, 1 H-[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-py ridine-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.
Hanania
T
T
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston 77555-1031, USA.
Johnson
K M
KM
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D002250:Carbon Radioisotopes; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009557:Nipecotic Acids / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019335:Nitroarginine / Q000494:pharmacology; D010091:Oximes / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014316:Tritium; D005680:gamma-Aminobutyric Acid / Q000187:drug effects / Q000378:metabolism
D002250:Carbon Radioisotopes; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D018756:GABA Antagonists; D018377:Neurotransmitter Agents; D009557:Nipecotic Acids; D010091:Oximes; D014316:Tritium; C078793:NNC 711; D019335:Nitroarginine; D009569:Nitric Oxide; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D000109:Acetylcholine