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. and Wonnacott, S., 2004. Functional responses and subunit composition of presynaptic nicotinic receptor subtypes explored using the novel agonist 5-iodo-A-85380. Neuropharmacology, 47 (6), pp. 848-859.
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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.
|Creators||Mogg, A. J., Jones, F. A., Pullar, I. A., Sharples, C. G. V. and Wonnacott, S.|
|Departments||Faculty of Science > Biology & Biochemistry|
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