Document Detail


Comparison of the effects of bupropion on nicotinic receptor-evoked [(3)H]dopamine release from rat striatal synaptosomes and slices.
MedLine Citation:
PMID:  17477919     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Tobacco smoking is a nicotine addiction, mediated in part by the ability of nicotine to elicit dopamine release, as a result of the stimulation of nicotinic acetylcholine receptors associated with dopaminergic pathways. The smoking cessation agent bupropion is an inhibitor of the dopamine transporter, but has also been shown to inhibit nicotinic acetylcholine receptors. To assess the relative impact of its actions at these two targets, we have examined the effects of bupropion on nicotine-evoked [(3)H]dopamine release from rat striatal synaptosomes and slices, in the absence of any other transporter inhibitor. Bupropion (10 microM) significantly decreased nicotine-evoked [(3)H]dopamine release by approximately 50% in both preparations, consistent with the blockade of nicotinic receptors. In support of this interpretation, bupropion also selectively inhibited nicotine-evoked Ca(2+) increases in SH-SY5Y cells. In striatal slices (but not in synaptosomes) the concentration-response profile for bupropion has an inverted 'u' shape, with a decrease in nicotine-evoked [(3)H]dopamine release also observed in the presence of 0.1 microM bupropion. This effect of 0.1 microM bupropion (but not 10 microM bupropion) was reversed by the dopamine D(2) receptor antagonist raclopride. We propose that modest blockade of the dopamine transporter by low concentrations of bupropion results in feedback inhibition via dopamine D(2) autoreceptors. This is overcome at higher concentrations of bupropion, before inhibition of nicotinic receptors occurs. Therefore bupropion's inhibition of the dopamine transporter and nicotinic receptors appears to be separated with respect to concentration.
Authors:
Nimish Sidhpura; Peter Redfern; Susan Wonnacott
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Publication Detail:
Type:  Comparative Study; In Vitro; Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-04-06
Journal Detail:
Title:  European journal of pharmacology     Volume:  567     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2007 Jul 
Date Detail:
Created Date:  2007-05-28     Completed Date:  2007-07-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  102-9     Citation Subset:  IM    
Affiliation:
Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK.
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MeSH Terms
Descriptor/Qualifier:
Animals
Bupropion / pharmacology*
Calcium / metabolism
Cell Line
Corpus Striatum / drug effects*,  metabolism,  ultrastructure
Dopamine / metabolism*
Dopamine Plasma Membrane Transport Proteins / antagonists & inhibitors*
Male
Nicotine / pharmacology
Nicotinic Agonists / pharmacology
Nicotinic Antagonists / pharmacology
Rats
Rats, Sprague-Dawley
Receptors, Nicotinic / drug effects*,  physiology
Synaptosomes / drug effects*,  metabolism
Chemical
Reg. No./Substance:
0/Dopamine Plasma Membrane Transport Proteins; 0/Nicotinic Agonists; 0/Nicotinic Antagonists; 0/Receptors, Nicotinic; 34841-39-9/Bupropion; 54-11-5/Nicotine; 7440-70-2/Calcium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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