Noncholinergic, Saturable Binding of (±)-[³H]Nicotine to Mouse Brain

Abstract

(±)-[³H]Nicotine was bound saturably to crude particulate, and synaptosomal - mitochondrial fractions from mouse brain. Scatchard and Hill plots of the binding data are in agreement with the existence of two independent classes of binding sites with high (K_d of 0.1 - 0.4 μM) and low (k_d is 20 μM) affinities, although negative cooperativity or a two-step model of ligand-receptor interaction cannot be ruled out. Nicotinic or muscarinic agonists and antagonists had little or no affinity for the nicotine binding sites, suggesting that nicotine binds in brain to noncholinergic sites. The binding did not display stereospecificity; this is consistent with the similarity in the pharmacological effects of (-)-and (+)-nicotine. Our results indicate that binding studies with [³H]nicotine should be interpreted with extreme caution.