Expression and functional characterisation of a human chimeric nicotinic receptor with α6β4 properties

被引：34

作者：

Evans, NM ^{[1
]}

Bose, S ^{[1
]}

Benedetti, G ^{[1
]}

Zwart, R ^{[1
]}

Pearson, KH ^{[1
]}

McPhie, GI ^{[1
]}

Craig, PJ ^{[1
]}

Benton, JP ^{[1
]}

Volsen, SG ^{[1
]}

Sher, E ^{[1
]}

Broad, LM ^{[1
]}

机构：

[1] Eli Lilly & Co Ltd, Lilly Res Ctr, Windlesham GU20 6PH, Surrey, England

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 2003年 / 466卷 / 1-2期

关键词：

nicotinic receptor; alpha; 6; subunit; chimera; HEK-293; cell; (human);

D O I：

10.1016/S0014-2999(03)01540-1

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Despite being cloned several years ago, the expression of functional nicotinic acetylcholine receptors containing the human alpha6 subunit in recombinant mammalian cell lines has yet to be demonstrated. The resulting lack of selective ligands has hindered the evaluation of the role of alpha6-containing nicotinic receptors. We report that functional channels were recorded following co-transfection of human embryonic kidney (HEK-293) cells with a chimeric alpha6/alpha4 subunit and the beta4 nicotinic receptor subunit. They displayed an agonist rank order potency of epibatidine much greater than 1,1-dimethyl-4-phenylpiperazinium (DMPP) greater than or equal to cytisine>acetylcholine>nicotine measured in a fluorescent imaging plate reader assay. Nicotine, cytisine, DMPP and epibatidine displayed partial agonist properties whilst alpha-conotoxin MII and methyllycaconitine blocked the functional responses elicited by acetylcholine stimulation. Co-transfection of the alpha6/alpha4 chimera with the 2 nicotinic receptor subunit did not result in functional receptors. The human alpha6/alpha4beta4 chimeric nicotinic receptor expressed in HEK-293 cells may provide a valuable tool for the generation of subtype specific ligands. (C) 2003 Elsevier Science B.V. All rights reserved.

引用

页码：31 / 39

页数：9

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