Nicotinic receptors in mammalian brain.

Nicotine has marked effects on CNS function increasing brain excitability and spontaneous activity and also has antinociceptive actions. Agonist radioligands for the nicotinic cholinergic receptor bind with high affinity in a saturable manner. Binding is however, insensitive to the ganglionic blockers, hexamethonium and mecamylamine. This suggests that agonists and antagonists bind to different sites on the receptor or that the nicotinic receptor in brain is different from that found in peripheral tissues. The nicotinic antagonist, dihydro-beta-erythroidine binds with high affinity (Kd = 4 nM) to rat brain membranes in a stereospecific, saturable, manner with a regional distribution similar to that seen with radiolabeled acetylcholine. Binding is insensitive to hexamethonium and mecamylamine. It is concluded that the nicotinic recognition sites to which dihydro-beta-erythroidine binds are neuromuscular rather than ganglionic in nature.