Identification of a novel nicotinic binding site in mouse brain using [<sup>125</sup>I]‐epibatidine

British Journal of Pharmacology - Tập 131 Số 4 - Trang 729-739 - 2000
Paul Whiteaker1, Melissa Jimenez1, J. Michael McIntosh2,3, Allan C. Collins1, Michael J. Marks1
1Institute for Behavioral Genetics, University of Colorado, Boulder, Colorado, CO 80303 U.S.A.
2Department of Biology, University of Utah, Salt Lake City, Utah, UT 84112, U.S.A.
3Department of Psychiatry, University of Utah, Salt Lake City, Utah, UT 84112, U.S.A.

Tóm tắt

[125I]‐Epibatidine binds to multiple nicotinic acetylcholine receptor (nAChR) subtypes with high affinity. In this study, [125I]‐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 [125I]‐epibatidine was saturable and apparently monophasic in each brain region (KD=71±12 pM mean±s.e.mean across regions) but inhibition of [125I]‐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 [125I]‐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 [125I]‐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 (−)‐[3H]‐nicotine‐, [125I]‐α‐bungarotoxin‐, or [125I]‐α‐conotoxin MII‐binding sites, suggesting that they represent a novel nAChR population in mouse brain. British Journal of Pharmacology (2000) 131, 729–739; doi:10.1038/sj.bjp.0703616

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British Journal of Pharmacology

Tập 131 Số 4

729-739

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