Functional responses and subunit composition of presynaptic nicotinic receptor subtypes explored using the novel agonist 5-iodo-A-85380

A J Mogg, F A Jones, I A Pullar, C G V Sharples, S Wonnacott

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Abstract

The novel compound 5-iodo-A-85380 binds with higher affinity to alpha4beta2* nicotinic acetylcholine receptors (nAChR), compared with other nAChR subtypes (Mukhin et al., 2000). In the present study, we have confirmed that in competition binding assays for three major nAChR subtypes, 5-iodo-A-85380 is 850 and 27,000-fold more potent at rat brain alpha4beta2* binding sites than at alpha3beta4 and alpha subtypes, respectively. In functional assays, 5-iodo-A-85380 potently activated (EC50 12-35 nM) both alpha-CTx-MII-sensitive and -insensitive components of [H-3]dopamine release from rat striatal synaptosomes, corresponding to alpha6beta2* and alpha4beta2* nAChR, respectively. 5-Iodo-A-85380 was markedly less potent at eliciting [H-3]ACh release from rat interpeduncular nucleus synaptosomes, [3H]noradrenaline release from rat hippocampal slices, and Ca2+ increases in a cell line expressing rat alpha3beta4 nAChR (EC50 = 5, 3.2, 1.6 muM, respectively). As predicted by ligand binding studies, 5-iodo-A-85380 is a more discriminating agonist than the parent compound epibatidine. However, it is not specific for alpha4beta2* nAChR as it also potently activates alpha6beta2* nAChR.
LanguageEnglish
Pages848-859
Number of pages12
JournalNeuropharmacology
Volume47
Issue number6
DOIs
StatusPublished - Nov 2004

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A 85380
Presynaptic Receptors
Nicotinic Receptors
epibatidine
Synaptosomes
Corpus Striatum
Dopamine
Norepinephrine
Binding Sites
Ligands
Cell Line
Brain
nicotinic receptor alpha4beta2

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Functional responses and subunit composition of presynaptic nicotinic receptor subtypes explored using the novel agonist 5-iodo-A-85380. / Mogg, A J; Jones, F A; Pullar, I A; Sharples, C G V; Wonnacott, S.

In: Neuropharmacology, Vol. 47, No. 6, 11.2004, p. 848-859.

Research output: Contribution to journalArticle

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