Open AccessTacrine Increases Stimulation-Evoked Acetylcholine Release from Rat Hippocampal Slices
Author(s) -
Takeshi Suzuki,
Hikaru aka,
Kazuko Fujimoto,
Koichiro Kawashima
Publication year - 1994
Publication title -
japanese journal of pharmacology/japanese journal of pharmacology
Language(s) - Uncategorized
Resource type - Journals
eISSN - 1347-3506
pISSN - 0021-5198
DOI - 10.1254/jjp.65.337
Subject(s) - tacrine , physostigmine , atropine , acetylcholine , cholinesterase , chemistry , stimulation , cholinergic , muscarinic acetylcholine receptor , pharmacology , endocrinology , medicine , acetylcholinesterase , biochemistry , receptor , enzyme
We examined the effects of tacrine (9-amino-1,2,3,4-tetrahydroacridine) on endogenous acetylcholine (ACh) release from rat hippocampal slices. Tacrine (more than 1 microM) increased the measurable amount of basal ACh release. On the other hand, in the presence of physostigmine (50 microM; under this condition, cholinesterase activity was inhibited), tacrine did not enhance the basal ACh release. Tacrine at more than 100 microM increased the submaximal electrical stimulation-evoked release of ACh in both the absence and presence of physostigmine (50 microM). This effect of tacrine was abolished by a combination of atropine (100 mM) and physostigmine. These results indicate that a high-dose of tacrine increases cholinergic neurotransmission not only by inhibition of cholinesterase but also by increasing ACh release through an atropine-like effect, perhaps by blockade of part of the process of muscarinic autoinhibition.