[³H]Acetylcholine nicotinic recognition sites in human brain: Characterization of agonist binding

In the presence of a cholinesterase inhibitor to prevent hydrolysis and atropine to block muscarinic cholinergic receptors, [³H]acetylcholine ([³H]ACh) binding to human brain membranes showed highest levels of nicotinic binding sites in the thalamus. [³H]ACh, in the presence of atropine, binds to heterogenous high-affinity binding sites in human thalamus. Scatchard analysis of the binding gave a K_d of 0.58 nM and a B_max of 3.3 pmol/g protein for the 'super high-affinity' site and a K_d of 27 nM and a B_max of 70 pmol/g protein for the 'high-affinity' site. Moreover, in competition studies nicotinic agonists such (-)-nicotine and carbachol displaceable [³H]ACh-specific binding sites consist of both a high- and a low-affinity population of sites. These results indicate that highest levels of [³H]ACh binding in human brain were found in the thalamus. Moreover, the human thalamus was found to have multiple high-affinity nicotinic agonist sites.