Heterogeneity of Brain Nicotine Receptors: A Functional Approach

Abstract

To study nicotinic receptors in the brain, we have compared the biochemical and pharmacological properties of ligand binding sites with a model in which receptor function can be measured. The system is based on the nicotinic facilitation of dopamine release from striatal nerve terminals, and we have demonstrated the release of [3H]dopamine from perfused synaptosomes in response to sub_µmolar concentrations of nicotinic agonists (1). This nicotinic mechanism is antagonized by ganglionic antagonists and the shellfish toxin neosurugatoxin, but not α-bungarotoxin (2). Although ligand binding is generally unaffected by many antagonists, high affinity [3H]nicotine binding to whole brain membranes is sensitive to dihydro-β-erythroidine and neosurugatoxin, but not α-bungarotoxin (2). However, [125I]α-bungarotoxin binding is not inhibited by neosurugatoxin, although it is sensitive to higher concentrations of nicotine and dihydro-β-erythroidine.