[125I]Iodomethyllycaconitine binds to α7 nicotinic acetylcholine receptors in monkey brain

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We examined the binding of the novel nicotinic acetylcholine receptor (nAChR) ligand [125I]iodomethyllycaconitine (iodoMLA) in the brains of M. cynomologous (macaque) monkeys. [125I]iodoMLA bound throughout the brain with the greatest density in the thalamus and moderate intensity in the basal ganglia and cortical regions. The Kd and Bmax in whole brain tissue were similar whether 1 mM nicotine (Kd 33.25 ± 15.17 nM, Bmax 5.80 ± 1.06 fmol/mg) or 2 μM of the α7-selective antagonist α-bungarotoxin (Kd 46.12 ± 18.45 nM, Bmax 6.30 ± 1.06 fmol/mg) was used for nonspecific binding. The subtype-selectivity of this ligand was further studied with competition binding studies using nicotine, α-bungarotoxin and noniodinated MLA. Each ligand completely inhibited [125I]iodoMLA binding throughout the monkey brain, with Ki values of 2.23 ± 0.85 μM for nicotine, 2.72 ± 1.71 nM for α-bungarotoxin and 1.83 ± 0.35 nM MLA in the caudate and 2.03 ± 1.14 μM, 2.65 ± 0.86 nM and 3.32 ± 0.71 nM, respectively, in the putamen. The α3β2/α6*-selective antagonist α-conotoxin MII failed to inhibit [125I]iodoMLA binding in any brain region. In monkeys with cognitive deficits resulting from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration, [125I]iodoMLA binding was significantly increased in the striatum, similar to results previously observed for [125I]α-bungarotoxin. These results suggest that, under the present experimental conditions, [125I]iodoMLA was selective for α7-containing nAChRs and did not bind to α6-containing nAChRs. This radioligand may be a useful tool for selectively imaging α7-containing nAChRs in vivo.

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