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Vol. 54, Issue 6, 1132-1139, December 1998
2 and 4 Subunits Confer Large
Differences in Agonist Binding Affinity
Department of Molecular and Cellular Pharmacology, University of
Miami School of Medicine, Miami, Florida 33101
We used equilibrium binding analysis to characterize the agonist
binding properties of six different rat neuronal nicotinic receptor
subunit combinations expressed in Xenopus laevis
oocytes. The 
4
2 receptor bound [3H]cytisine with a
Kdapp of 0.74 ± 0.14 nM. The rank order of
Kiapp values of
additional nicotinic ligands, determined in competition assays, was
cytisine < nicotine < acetylcholine < carbachol < curare. These pharmacological properties of 42 expressed in
oocytes are comparable to published values for the high affinity
cytisine binding site in rat brain (42), demonstrating that rat
neuronal nicotinic receptors expressed in X.
laevis oocytes display appropriate pharmacological
properties. Use of [3H]epibatidine allowed detailed
characterization of multiple neuronal nicotinic receptor subunit
combinations. Kdapp
values for [3H]epibatidine binding were 10 pM for 22, 87 pM for 24,
14 pM for 32, 300 pM for
34, 30 pM for 42, and 85 pM for 44. Affinities for six additional
agonists (acetylcholine, anabasine, cytisine,
1,1-dimethyl-4-phenylpiperazinium, lobeline, and nicotine) were
determined in competition assays. The 2-containing receptors had
consistently higher affinities for these agonists than did 4-containing receptors. Particularly striking examples are the affinities displayed by 22 and 24, which differ in
1,1-dimethyl-4-phenylpiperazinium, nicotine, lobeline, and
acetylcholine affinity by 120-, 86-, 85-, and 61-fold, respectively.
Although smaller differences in affinity could be ascribed to different
subunits, the major factor in determining agonist affinity was the
nature of the subunit.
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