This report describes the membrane binding properties of [3H] hemicholinium-3 ([3H]HC-3), a selective inhibitor of sodium-dependent high-affinity choline uptake (SDHACU) in cholinergic nerve terminals. Under the described assay conditions, [3H]HC-3 binds with a saturable population of high-affinity (apparent Kd=1.9 nM) CNS membrane sites having the regional distribution: striatum ≫ hippocampus > cerebral cortex > cerebellum. High-affinity [3H]HC-3 binding is entirely dependent upon the presence of sodium chloride (EC50=35-50 mM) and is markedly reduced when other salts of sodium or monovalent ions are substituted. [3H]HC-3 binding is inhibited by choline (Ki=6μM) and acetylcholine (Ki=35μM) but markedly less sensitive to other cholinergic agents and metabolic inhibitors. In light of the similar ionic dependencies, regional distributions and pharmacological specificities of [3H]HC-3 binding and SDHACU, closely associated sites may be involved in both processes.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Pharmacology, Toxicology and Pharmaceutics(all)