Enhancement of [3H]dopamine release and its [3H]metabolites in rat striatum by nicotinic drugs.
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.
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D015098:3-Methoxy-4-hydroxyphenylethanol / Q000378:metabolism; D008735:5-Methoxytryptamine / Q000378:metabolism; D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005731:Ganglionic Stimulants / Q000494:pharmacology*; D008297:Male; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011978:Receptors, Nicotinic / Q000502:physiology; D013574:Synaptosomes / Q000378:metabolism
D005731:Ganglionic Stimulants; D011978:Receptors, Nicotinic; D015102:3,4-Dihydroxyphenylacetic Acid; C005975:3,4-dihydroxyphenylethanol; D015098:3-Methoxy-4-hydroxyphenylethanol; D008735:5-Methoxytryptamine; D010626:Phenylethyl Alcohol; D004298:Dopamine