Presynaptic alpha 7 and non-alpha 7 nicotinic acetylcholine receptors modulate [H-3]D-aspartate release from rat frontal cortex in vitro

S J Rousseau, I W Jones, I A Pullar, S Wonnacott

Research output: Contribution to journalArticlepeer-review

72 Citations (Scopus)

Abstract

The presynaptic nicotinic modulation of glutamatergic transmission in the CNS has been associated with activation of the alpha 7 subtype of nicotinic acetylcholine receptor (nAChR) in sub-cortical regions, whereas in the frontal cortex, non-alpha 7 nAChRs have been implicated. The aim of this investigation was to directly characterise nAChR-evoked release of excitatory amino acids from rat frontal cortex, by monitoring the release of [H-3]D-aspartate from superfused synaptosomes or minces. Co-administration of a nAChR agonist with a depolarising stimulus enhanced [H-3]D-aspartate release above the effect of depolarising agent alone. This enhancement was blocked by the nicotinic antagonist mecamylamine. Other experiments revealed that in the absence of a depolarising stimulus, the nAChR agonists nicotine, epibatidine and anatoxin-a could evoke the release of [H-3]D-aspartate in a Ca2+ - and concentration-dependant manner. Differential sensitivity to the alpha 7- and beta 2*-selective nAChR antagonists alpha-bungarotoxin (alpha-Bgt) and dihydro-beta-erythroidine (DH beta E) implicated two nAChR subtypes (alpha 7 and beta 2*), and this was supported by using the subtype-selective agonists choline (10 mM; alpha 7 selective, blocked by alpha-Bgt but not by DH beta E) and 5-lodo-A-85380 (10nM; beta 2*-selective, blocked by DH beta E but not by alpha-Bgt). Immunocytochemistry showed that alpha-Bgt labelling was associated with structures immunopositive for vesicular glutamate transporters, in both frontal cortex sections and synaptosome preparations, supporting the presence of alpha 7 nAChR on glutamatergic terminals in rat frontal cortex.
Original languageEnglish
Pages (from-to)59-72
Number of pages14
JournalNeuropharmacology
Volume49
Issue number1
DOIs
Publication statusPublished - Jul 2005

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