Nicotinic stimulation of [3H]acetylcholine release from mouse cerebral cortical synaptosomes.
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 potassium. 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%) calcium-dependent. Nicotine also produced an increase in [3H]choline accumulation into synaptosomes. These results indicate that the nicotinic agonists nicotine and DMPP can produce a moderate enhancement of acetylcholine release by a receptor-mediated action on cholinergic nerve terminals in the central nervous system.
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D002794:Choline / Q000378:metabolism; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology*; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D051379:Mice; D009538:Nicotine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D013574:Synaptosomes / Q000378:metabolism*
D006584:Hexamethonium Compounds; D010879:Piperazines; D018738:Hexamethonium; D004246:Dimethylphenylpiperazinium Iodide; D009538:Nicotine; D002794:Choline; D000109:Acetylcholine; D011188:Potassium