Effect of nicotine and tacrine on acetylcholine release from rat cerebral cortical slices |
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Authors: | R E Loiacono F J Mitchelson |
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Institution: | (1) School of Pharmacology, Victorian College of Pharmacy, 381Royal Pde, 3052 Parkville, Victoria, Australia |
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Abstract: | Summary The effect of nicotine (1–10 M) and tacrine (9-amino-1,2,3,4-tetrahydroacridine; THA) on stimulation evoked release of 3H]acetylcholine from the rat brain slice preparation preincubated with 3H]choline was investigated.In these preparations, nicotine enhanced while tacrine inhibited evoked 3H]acetylcholine release. These effects were blocked by (+)tubocurarine (1 M) and atropine (0.1 M) respectively. In the presence of idazoxan (0.3 M) plus atropine (0.1 M), nicotine (3 M) continued to enhance evoked 3H]acetylcholine release while the inhibitory effect of tacrine (1 M) on evoked 3H]acetylcholine release was reversed to an enhancement. Under these circumstances the effects of both nicotine and tacrine were blocked by (+)tubocurarine (1 M).These findings demonstrate that tacrine can both inhibit or enhance 3H]acetylcholine release, most likely through its activity as a cholinesterase inhibitor. Under normal circumstances following tacrine the predominant effect of the elevated levels of acetylcholine will be activation of inhibitory presynaptic muscarine receptors on cholinergic nerves and an inhibition of evoked 3H]acetylcholine release. Under conditions where both presynaptic inhibitory muscarine and 2-adrenoceptors are blocked, the elevated levels of acetylcholine produced by tacrine will lead to the activation of facilitatory presynaptic nicotine cholinoceptors on cholinergic nerves and an enhancement of evoked 3H]acetylcholine release.
Send offprint requests to R. Loiacono at the above address |
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Keywords: | [3H]Acetylcholine release Presynaptic nicotine cholinoceptors Tacrine THA Cerebral cortex |
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