![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
|
|
|
|
|
||
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Received for publication August 23, 2004.
Revised January 28, 2005.
Accepted for publication January 28, 2005.
6* nAChR sites and function in mice
-Conotoxin MII-sensitive nicotinic receptors (nAChRs) are distinct from other subtypes in their relatively restricted localization to the striatum and some other brain regions. The effect of nicotine treatment on nAChR subtypes has been extensively investigated, with the exception of changes in -conotoxin MII-sensitive receptor expression. We therefore determined the consequence of chronic nicotine administration on this subtype and its function. Nicotine was given in drinking water to provide a chronic yet intermittent treatment. Consistent with previous studies, nicotine exposure increased 125I-epibatidine and 125I-A85380, but not 125I--bungarotoxin, receptors in cortex and striatum. Unexpectedly, we observed a decrease (30%) in striatal 125I--conotoxin MII sites, which was due to a decrease in Bmax. This decline was more robust in older (>8 month) compared to younger (2-4 month) mice, suggesting age is important for nicotine-induced disruption of nAChR phenotype. Immunoprecipitation experiments using nAChR subunit-directed antibodies indicate that alterations in subunit-immunoreactivity with nicotine treatment agree with changes observed in the receptor binding studies. To determine the relationship between striatal nAChR sites and function, we measured nicotine-evoked 3H-dopamine release. A decline was obtained with nicotine treatment that was due to a selective decrease in -conotoxin MII-sensitive but not -resistant dopamine release. These results may explain earlier findings that nicotine treatment decreased striatal nAChR-mediated dopamine function, despite an increase in 3H-nicotine (4*) sites. The present data suggest that the 6* nAChR subtype represents a key factor in the control of dopamine release from striatum, which adapts to chronic nicotine treatment by down-regulation of 6* receptor sites and function.
Key words:
Nicotinic cholinergic, Func. analysis receptor/ion channel mutants, Immunocytochemistry, Receptor binding studies
This article has been cited by other articles:
|
|
 |
|
  T. Bordia, C. Campos, L. Huang, and M. Quik Continuous and Intermittent Nicotine Treatment Reduces L-3,4-Dihydroxyphenylalanine (L-DOPA)-Induced Dyskinesias in a Rat Model of Parkinson's Disease J. Pharmacol. Exp. Ther., October 1, 2008; 327(1): 239 - 247. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. A. Perez, T. Bordia, J. M. McIntosh, S. R. Grady, and M. Quik Long-Term Nicotine Treatment Differentially Regulates Striatal {alpha}6{alpha}4{beta}2* and {alpha}6(Non{alpha}4){beta}2* nAChR Expression and Function Mol. Pharmacol., September 1, 2008; 74(3): 844 - 853. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Azam, D. Yoshikami, and J. M. McIntosh Amino Acid Residues That Confer High Selectivity of the {alpha}6 Nicotinic Acetylcholine Receptor Subunit to {alpha}-Conotoxin MII[S4A,E11A,L15A] J. Biol. Chem., April 25, 2008; 283(17): 11625 - 11632. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Walsh, A. P. Govind, R. Mastro, J. C. Hoda, D. Bertrand, Y. Vallejo, and W. N. Green Up-regulation of Nicotinic Receptors by Nicotine Varies with Receptor Subtype J. Biol. Chem., March 7, 2008; 283(10): 6022 - 6032. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. C. Perry, D. Mao, A. B. Gold, J. M. McIntosh, J. C. Pezzullo, and K. J. Kellar Chronic Nicotine Differentially Regulates {alpha}6- and beta3-Containing Nicotinic Cholinergic Receptors in Rat Brain J. Pharmacol. Exp. Ther., July 1, 2007; 322(1): 306 - 315. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Bordia, N. Parameswaran, H. Fan, J. W. Langston, J. M. McIntosh, and M. Quik Partial Recovery of Striatal Nicotinic Receptors in 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-Lesioned Monkeys with Chronic Oral Nicotine J. Pharmacol. Exp. Ther., October 1, 2006; 319(1): 285 - 292. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Tumkosit, A. Kuryatov, J. Luo, and J. Lindstrom beta3 Subunits Promote Expression and Nicotine-Induced Up-Regulation of Human Nicotinic {alpha}6* Nicotinic Acetylcholine Receptors Expressed in Transfected Cell Lines Mol. Pharmacol., October 1, 2006; 70(4): 1358 - 1368. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. McCallum, N. Parameswaran, T. Bordia, H. Fan, J. M. McIntosh, and M. Quik Differential Regulation of Mesolimbic {alpha}3/{alpha}6beta2 and {alpha}4beta2 Nicotinic Acetylcholine Receptor Sites and Function after Long-Term Oral Nicotine to Monkeys J. Pharmacol. Exp. Ther., July 1, 2006; 318(1): 381 - 388. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Quik, L. Chen, N. Parameswaran, X. Xie, J. W. Langston, and S. E. McCallum Chronic oral nicotine normalizes dopaminergic function and synaptic plasticity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned primates. J. Neurosci., April 26, 2006; 26(17): 4681 - 4689. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Quik and J. M. McIntosh Striatal {alpha}6* Nicotinic Acetylcholine Receptors: Potential Targets for Parkinson's Disease Therapy J. Pharmacol. Exp. Ther., February 1, 2006; 316(2): 481 - 489. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
