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PMID: 11030722 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Identification of a novel nicotinic binding site in mouse brain using [(125)I]-epibatidine.

British journal of pharmacology ·Vol. 131 ·No. 4 ·2000-10-00 ·Pages 729-39

Whiteaker P, Jimenez M, McIntosh JM, Collins AC, Marks MJ

Abstract

[(125)I]-Epibatidine binds to multiple nicotinic acetylcholine receptor (nAChR) subtypes with high affinity. In this study, [(125)I]-epibatidine was used to label and characterize a novel nAChR subtype found in mouse brain inferior colliculus, interpeduncular nucleus, and olfactory bulb homogenates. Binding of [(125)I]-epibatidine was saturable and apparently monophasic in each brain region (K:(D:)=71+/-12 pM mean+/-s.e.mean across regions) but inhibition of [(125)I]-epibatidine binding (200 pM) by A85380, cytisine and (-)-nicotine was biphasic, indicating the presence of multiple binding sites. The sites with lower agonist affinity comprised 30.0+/-2.2, 58.6+/-0.1 and 48.7+/-3.3% of specific [(125)I]-epibatidine (200 pM) binding in inferior colliculus, interpeduncular nucleus, and olfactory bulb homogenates, respectively. The affinity difference between A85380-sensitive and -resistant binding sites was particularly marked (approximately 1000 fold). Thus A85380 was used to differentiate agonist-sensitive and -resistant sites. The pharmacological profiles of the A85380-resistant sites in each region were assessed with inhibition binding experiments, using 14 agonists and five antagonists. The profiles were indistinguishable across regions, implying that A85380-resistant [(125)I]-epibatidine binding sites in inferior colliculus, interpeduncular nucleus, and olfactory bulb represent a single nAChR subtype. The pharmacological profile of the A85380-resistant sites is very different from that previously reported for high affinity (-)-[(3)H]-nicotine-, [(125)I]-alpha-bungarotoxin-, or [(125)I]-alpha-conotoxin MII-binding sites, suggesting that they represent a novel nAChR population in mouse brain.

MeSH Terms
Alkaloids/pharmacology Animals Autoradiography Azetidines/metabolism Azocines Binding Sites Brain/metabolism Bridged Bicyclo Compounds, Heterocyclic/metabolism Iodine Radioisotopes Male Mice Mice, Inbred C57BL Nicotine/metabolism Nicotinic Agonists/metabolism Pyridines/metabolism Quinolizines Receptors, Nicotinic/analysis,metabolism
Chemicals
A 85380 Alkaloids Azetidines Azocines Bridged Bicyclo Compounds, Heterocyclic Iodine Radioisotopes Nicotinic Agonists Pyridines Quinolizines Receptors, Nicotinic cytisine Nicotine epibatidine
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Whiteaker P
Institute for Behavioral Genetics, University of Colorado, Boulder, Colorado, CO 80303 USA.
Jimenez M
McIntosh J M
Collins A C
Marks M J
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Article Info
Journal
British journal of pharmacology
Abbr.
Br J Pharmacol
ISSN
0007-1188
DOI
10.1038/sj.bjp.0703616
Published
2000-10-00
Pages
729-39
Language
English
Region
England
NLM ID
7502536
PMCID
PMC1572375
Subset
IM
Grants
NIDA NIH HHS · DA-10156 · United States
NIDA NIH HHS · R01 DA003194 · United States
NIDA NIH HHS · R01 DA012242 · United States
NIGMS NIH HHS · P01 GM048677 · United States
NIMH NIH HHS · R01 MH053631 · United States
NIMH NIH HHS · R29 MH053631 · United States
NIDA NIH HHS · DA-12242 · United States
NIDA NIH HHS · DA-03194 · United States
External Links
PubMed source DOI: 10.1038/sj.bjp.0703616 PMC Full Text View journal details
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