Document Detail

Pharmacological properties of alpha 9 alpha 10 nicotinic acetylcholine receptors revealed by heterologous expression of subunit chimeras.
MedLine Citation:
PMID:  14742688     Owner:  NLM     Status:  MEDLINE    
The nicotinic acetylcholine receptor (nAChR) alpha9 and alpha10 subunits are expressed primarily within hair cells of the inner ear and have been implicated in auditory processing. Although functional recombinant nAChRs generated by the coexpression of alpha9 and alpha10 in Xenopus laevis oocytes have been described previously, there have been no reports of the successful heterologous expression of alpha9alpha10 nAChRs in cultured cell lines. In this study, subunit chimeras (alpha9chi and alpha10chi) have been constructed that contain the extracellular, ligand binding domain of the alpha9 or alpha10 subunits fused to the C-terminal domain of the 5-hydroxytryptamine type 3A (5HT3A) subunit. Specific high-affinity binding of the nicotinic radioligand [3H]methyllycaconitine was detected in membrane preparations of mammalian cells transfected with alpha9chi or alpha10chi alone, but significantly higher levels of binding were detected when alpha9chi and alpha10chi were cotransfected, providing evidence of a requirement for coassembly of alpha9 and alpha10 for the efficient formation of a nicotinic binding site. The pharmacological profile of alpha9chialpha10chi receptors, determined by equilibrium radioligand binding studies, is broadly similar to that determined previously by electrophysiological studies conducted with native and recombinant alpha9alpha10 nAChRs. In agreement with evidence that alpha9alpha10 nAChRs exhibit an atypical pharmacological profile, we have identified specific high-affinity binding of several non-nicotinic ligands including strychnine (a glycine receptor antagonist), bicuculline (a GABAA receptor antagonist), and atropine (a muscarinic acetylcholine receptor antagonist). Results have also been compared with radioligand binding data conducted with a previously described alpha7/5HT3A (alpha7chi) subunit chimera.
Elizabeth R Baker; Ruud Zwart; Emanuele Sher; Neil S Millar
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular pharmacology     Volume:  65     ISSN:  0026-895X     ISO Abbreviation:  Mol. Pharmacol.     Publication Date:  2004 Feb 
Date Detail:
Created Date:  2004-01-26     Completed Date:  2004-03-12     Revised Date:  2008-10-01    
Medline Journal Info:
Nlm Unique ID:  0035623     Medline TA:  Mol Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  453-60     Citation Subset:  IM    
Department of Pharmacology, University College London, Gower Street, London, United Kingdom.
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MeSH Terms
Aconitine / analogs & derivatives*,  metabolism,  pharmacology
Cell Line
Chimera / genetics,  metabolism*
Dose-Response Relationship, Drug
Gene Expression Regulation / drug effects*,  physiology
Protein Binding / drug effects,  physiology
Protein Subunits / antagonists & inhibitors,  metabolism*
Receptors, Nicotinic / metabolism*
Xenopus laevis
Reg. No./Substance:
0/CHRNA9 protein, human; 0/Chrna10 protein, rat; 0/Chrna9 protein, mouse; 0/Chrna9 protein, rat; 0/Protein Subunits; 0/Receptors, Nicotinic; 21019-30-7/methyllycaconitine; 302-27-2/Aconitine

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