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Characterization of [ 125 I]epibatidine binding and nicotinic agonist‐mediated 86 Rb + efflux in interpeduncular nucleus and inferior colliculus of β2 null mutant mice
Author(s) -
Marks Michael J.,
Whiteaker Paul,
Grady Sharon R.,
Picciotto Marina R.,
McIntosh J. Michael,
Collins Allan C.
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2002.00910.x
Subject(s) - mecamylamine , epibatidine , cytisine , interpeduncular nucleus , nicotinic agonist , chemistry , inferior colliculus , agonist , pharmacology , nicotinic acetylcholine receptor , endocrinology , medicine , biology , biochemistry , nucleus , receptor , neuroscience , central nervous system , midbrain
The β2 nicotinic acetylcholine receptor subunit null mutation eliminated most high affinity [ 3 H]epibatidine binding in mouse brain, but significant binding remained in accessory olfactory nucleus, medial habenula, inferior colliculus and interpeduncular nucleus. Residual [ 125 I]epibatidine binding sites in the inferior colliculus and interpeduncular nucleus were subsequently characterized. Inhibition of [ 125 I]epibatidine binding by 12 agonists and six antagonists was very similar in these regions. Most acetylcholine‐stimulated 86 Rb + efflux is eliminated in thalamus and superior colliculus of β2 null mutants, but significant activity remained in inferior colliculus and interpeduncular nucleus. This residual activity was subsequently characterized. The 12 nicotinic agonists tested elicited concentration‐dependent 86 Rb + efflux. Epibatidine was the most potent agonist. Cytisine was also potent and efficacious. EC 50 values for quaternary agonists were relatively high. Cytisine‐stimulated 86 Rb + efflux was inhibited by six classical nicotinic antagonists. Mecamylamine and d ‐tubocurarine were most potent, while decamethonium was the least potent. Agonists and antagonists exhibited similar potency in both brain regions. α‐Bungarotoxin (100 n m ) did not significantly inhibit cytisine‐stimulated 86 Rb + efflux, while the α3β4 selective antagonist, αConotoxinAuIB, inhibited a significant fraction of the response in both brain regions. Thus, β2 null mutant mice express residual nicotinic activity with properties resembling those of α3β4*‐nAChR.