Abstract
Molecular genetic and pharmacological studies have suggested that several subtypes of nicotinic acetylcholine receptors exist in the mammalian and avian brain. Combining ^3^H‐(−)‐nicotine, ^125^ I‐α‐bungarotoxin, and ^125^I‐κ‐bungarotoxin as ligands, we report here the first evidence for the existence in human frontal cortex of at least three different subtypes of nicotinic receptors. Autoradiographic analysis shows that specific ^125^I‐κ‐bungarotoxin binding sites are concentrated mainly in several cortical layers. We also show that κ‐bungarotoxin, but not κ‐bungarotoxin decreases the evoked release of ^3^H‐acetylcholine in rat cortical slices, indicating a likely presynaptic localization for some of the α‐bungarotoxin‐insensitive κ‐bungarotoxin sites in mammalian brain. The brains of patients with Alzheimer's disease show marked decreases in B~max~ values for low‐affinity 125I‐κ‐bungarotoxin sites and both high‐ and low‐affinity ^3^H‐nicotine sites, whereas ^125^I‐κ‐bungarotoxin sites are not significantly different in number from age‐matched control brains. We conclude that Alzheimer's disease does not affect all subtypes of nicotinic receptors in the frontal cortex to the same extent.