Chronic Nicotine Differentially Regulates Alpha6- and Beta3-containing Nicotinic Cholinergic Receptors in Rat Brain.
From: Department of Pharmacology and Physiology, George Washington University, Washington, DC, USA.
The Journal of pharmacology and experimental therapeutics
- Publish Date: Jul 2007
- ISSN: 0022-3565
- Volume: 322
- Issue: 1
- Pages: 306-15
- Medium: Print
- Language: English
- Citation (JAMA): Perry David C, Mao Danyan, Gold Allison B, et al. Chronic Nicotine Differentially Regulates Alpha6- and Beta3-containing Nicotinic Cholinergic Receptors in Rat Brain.. J. Pharmacol. Exp. Ther. Jul 2007;322:306-15
Abstract
We investigated the effects of chronic nicotine on alpha6- and beta3-containing nicotinic acetylcholine receptors (nAChRs) in two rat brain regions using three methodological approaches: radioligand binding, immunoprecipitation, and nicotine-stimulated synaptosomal release of dopamine. Nicotine was administered by osmotic minipumps for 2 weeks. Quantitative autoradiography with [(125)I]alpha-conotoxin MII to selectively label alpha6(*) nAChRs showed a 28% decrease in binding in the striatum but no change in the superior colliculus. Immunoprecipitation of nAChRs labeled by [(3)H]epibatidine in these two regions showed that chronic nicotine increased alpha4- and beta2-containing nAChRs by 39 to 67%. In contrast, chronic nicotine caused a 39% decrease in alpha6-containing nAChRs in striatum but no change in superior colliculus. No changes in beta3-containing nAChRs were seen in either region after chronic nicotine. The decreased expression of alpha6-containing nAChRs persisted for at least 3 days, recovering to baseline by 7 days after removal of the pumps. There was a small but significant decrease in total nicotine-stimulated dopamine release in striatal synaptosomes after nicotine exposure. However, the component of dopamine release that was resistant to alpha-conotoxin MII blockade was unaffected, whereas dopamine release that was sensitive to blockade by alpha-conotoxin MII was decreased by 56%. These findings indicate that the alpha6(*) nAChR is regulated differently from other nAChR subtypes, and they suggest that the inclusion of a beta3 subunit with alpha6 may serve to inhibit nicotine-induced down-regulation of these receptors.
Mesh Headings (Keywords): Amino Acid Sequence, Animals, Autoradiography, Brain, Conotoxins, Dopamine, Immunoprecipitation, Male, Molecular Sequence Data, Nicotine, Rats, Rats, Sprague-Dawley, Receptors, Nicotinic
Check for Full Text / PubMed Unique Identifier (PMID): 17446303
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