Nicotinic Stimulation of [3H]Acetylcholine Release from Mouse Cerebral Cortical Synaptosomes

Abstract

The effects of nicotine and 1,1-dimethyl-4-phenylpiperazinium (DMPP) on the release of newly synthesized [3H]acetylcholine in mouse cerebral cortical synaptosomes were examined. Nicotine and DMPP produced increases in [3H]acetylcholine release, over the level of spontaneous release of 24 and 30%, respectively, of a maximum depolarization-induced release produced by 50 mM K. The maximum effect was achieved at a concentration of 1 x 10-4 M for both agents. The time course of release indicated a slow onset of action, reaching a maximum effect at 15 min of incubation. Both nicotine and DMPP also produced a slightly greater release of total tritium, measured in the absence of cholinesterase inhibition than of [3H]acetylcholine. The release induced by nicotine was completely antagonized by hexamethonium and was largely (58%) Ca-dependent. Nicotine also produced as increase in [3H]choline accumulation into synaptosomes. The nicotinic agonists nicotine and DMPP may produce a moderate enhancement of acetylcholine release by a receptor-mediated action on cholinergic nerve terminals in the CNS.