Enhancement of [3H]dopamine release and its [3H]metabolites in rat striatum by nicotinic drugs |
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Authors: | Y Sakurai Y Takano Y Kohjimoto K Honda H O Kamiya |
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Institution: | Department of Pharmacology, School of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-01 Japan |
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Abstract: | Recent evidence has identified directly muscarinic acetylcholine receptor (m-ACh R) and nicotinic acetylcholine receptor (n-ACh R) in the brain utilizing receptor binding assay. Several studies suggest that release of dopamine (DA) in the striatum is regulated by presynaptic receptors present on dopaminergic terminals. In the present study, the effects of cholinergic drugs on 3H]DA release were examined using micropunched tissue and synaptosomes obtained from rat striatum. ACh (5 x 10(-4) M) significantly increased spontaneous 3H]DA release, and the overflow was partially inhibited by D-tubocurarine (1 mM) but not atropine. Nicotine, lobeline, coniine and spartein, nicotinic agonists, significantly increased spontaneous and 25 mM K + evoked 3H]DA release almost in a dose-dependent manner. In contrast, oxotremorine (2 x 10(-4) M), muscarinic agonist, did not any change in 3H]DA efflux. Furthermore, the metabolites of 3H]DA were separated by column chromatography. The main metabolite of 3H]DA in the spontaneous release from rat striatal synaptosomes was 3H]DOPAC (3,4-dihydroxyphenylacetic acid). Lobeline (5 x 10(-5) M) accelerated the outflow of 3H]DOPAC and 3H]OMDA metabolites (O-methylated and deaminated metabolites). These results could give rise to the suggestion that there was n-ACh R on the dopaminergic nerve terminals in the striatum and n-ACh R might have related to a directly excitatory effect on the DA release. |
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Keywords: | dopamine release dopamine metabolism nicotinic drugs presynaptic nicotinic receptors lobeline |
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