Tacrine increases stimulation-evoked acetylcholine release from rat hippocampal slices.
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.
Suzuki
T
T
Department of Pharmacology, Kyoritsu College of Pharmacy, Tokyo, Japan.
Nonaka
H
H
Fujimoto
K
K
Kawashima
K
K
D000109:Acetylcholine / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D004558:Electric Stimulation; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects; D010830:Physostigmine / Q000494:pharmacology; D051381:Rats; D013619:Tacrine / Q000494:pharmacology*
D013619:Tacrine; D001285:Atropine; D010830:Physostigmine; D000109:Acetylcholine