MolPharm xPharm- The Comprehensive Pharmacology Reference

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Quik, M.
Right arrow Articles by Grady, S. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Quik, M.
Right arrow Articles by Grady, S. R.

Vol. 63, Issue 5, 1169-1179, May 2003

Differential Declines in Striatal Nicotinic Receptor Subtype Function after Nigrostriatal Damage in Mice

Maryka Quik, Jocelyn D. Sum, Paul Whiteaker, Sarah E. McCallum, Michael J. Marks, John Musachio, J. Michael Mcintosh, Allan C. Collins, and Sharon R. Grady

The Parkinson's Institute, Sunnyvale, California (M.Q., J.D.S.); Institute for Behavioral Genetics, University of Colorado, Boulder, Colorado (P.W., S.E.M., M.J.M., A.C.C., S.R.G.); Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland (J.M.); and Departments of Biology and Psychiatry, University of Utah, Salt Lake City, Utah (J.M.M.)

Nigrostriatal damage leads to a reduction in striatal nicotinic acetylcholine receptors (nAChRs) in rodents, monkeys, and patients with Parkinson's disease. The present studies were undertaken to investigate whether these nAChR declines are associated with alterations in striatal nAChR function and, if so, to identify the receptor subtypes involved. To induce nigrostriatal damage, mice were injected with the selective dopaminergic toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We measured [125I]3beta -(4-iodophenyl)tropane-2beta -carboxylic acid isopropyl ester (RTI-121, dopamine transporter), 125I-alpha -conotoxin MII (putative alpha 6-containing sites in the central nervous system), 125I-epibatidine (multiple sites), 5-[125I]iodo-3-[2(S)-azetidinylmethoxy]pyridine-2HCl ([125I]A85380; beta 2-containing sites), and 125I-alpha -bungarotoxin (alpha 7-containing sites) binding in brains from control and MPTP-treated mice, as well as nAChR function by [3H]dopamine release, [3H]GABA release, and [86Rb+] efflux. After MPTP treatment, declines were observed in striatal dopamine transporter levels, both binding and functional measures of striatal alpha -conotoxin MII-sensitive nAChRs, and selected measures of striatal alpha -conotoxin MII-resistant nAChRs. In contrast, 125I-alpha -bungarotoxin binding sites were not altered after nigrostriatal damage. The changes in striatal nAChRs were selective, with no declines in cortex, thalamus, or septum. Those striatal binding and functional measures of nAChRs that decreased with MPTP treatment correlated with dopamine transporter declines, an observation suggesting that the binding and functional changes in nAChRs are limited to dopaminergic terminals. The present results are the first to demonstrate differential alterations in nAChR subtype function after nigrostriatal damage, with a close correspondence between changes in receptor binding sites and function. These data suggest that the declines in nAChR sites observed in Parkinson's disease brains may be of functional significance.

Copyright © 2003 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 J. Pharmacol. Exp. Ther.Home page
K. T. O'Leary, N. Parameswaran, L. C. Johnston, J. M. McIntosh, D. A. Di Monte, and M. Quik
Paraquat Exposure Reduces Nicotinic Receptor-Evoked Dopamine Release in Monkey Striatum
J. Pharmacol. Exp. Ther., October 1, 2008; 327(1): 124 - 129.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
P. Whiteaker, M. J. Marks, S. Christensen, C. Dowell, A. C. Collins, and J. M. McIntosh
Synthesis and Characterization of 125I-{alpha}-Conotoxin ArIB[V11L;V16A], a Selective {alpha}7 Nicotinic Acetylcholine Receptor Antagonist
J. Pharmacol. Exp. Ther., June 1, 2008; 325(3): 910 - 919.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
T. Bordia, S. R. Grady, J. M. McIntosh, and M. Quik
Nigrostriatal Damage Preferentially Decreases a Subpopulation of {alpha}6beta2* nAChRs in Mouse, Monkey, and Parkinson's Disease Striatum
Mol. Pharmacol., July 1, 2007; 72(1): 52 - 61.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
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]

Home page
 Mol. Pharmacol.Home page
S. E. McCallum, N. Parameswaran, T. Bordia, J. M. McIntosh, S. R. Grady, and M. Quik
Decrease in {alpha}3*/{alpha}6* Nicotinic Receptors but Not Nicotine-Evoked Dopamine Release in Monkey Brain after Nigrostriatal Damage
Mol. Pharmacol., September 1, 2005; 68(3): 737 - 746.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
C. Gotti, M. Moretti, F. Clementi, L. Riganti, J. M. McIntosh, A. C. Collins, M. J. Marks, and P. Whiteaker
Expression of Nigrostriatal {alpha}6-Containing Nicotinic Acetylcholine Receptors Is Selectively Reduced, but Not Eliminated, by {beta}3 Subunit Gene Deletion
Mol. Pharmacol., June 1, 2005; 67(6): 2007 - 2015.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
A. Lai, N. Parameswaran, M. Khwaja, P. Whiteaker, J. M. Lindstrom, H. Fan, J. M. McIntosh, S. R. Grady, and M. Quik
Long-Term Nicotine Treatment Decreases Striatal {alpha}6* Nicotinic Acetylcholine Receptor Sites and Function in Mice
Mol. Pharmacol., May 1, 2005; 67(5): 1639 - 1647.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
M. Quik, S. Vailati, T. Bordia, J. M. Kulak, H. Fan, J. M. McIntosh, F. Clementi, and C. Gotti
Subunit Composition of Nicotinic Receptors in Monkey Striatum: Effect of Treatments with 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine or L-DOPA
Mol. Pharmacol., January 1, 2005; 67(1): 32 - 41.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
O. Salminen, K. L. Murphy, J. M. McIntosh, J. Drago, M. J. Marks, A. C. Collins, and S. R. Grady
Subunit Composition and Pharmacology of Two Classes of Striatal Presynaptic Nicotinic Acetylcholine Receptors Mediating Dopamine Release in Mice
Mol. Pharmacol., June 1, 2004; 65(6): 1526 - 1535.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
C. Cui, T. K. Booker, R. S. Allen, S. R. Grady, P. Whiteaker, M. J. Marks, O. Salminen, T. Tritto, C. M. Butt, W. R. Allen, et al.
The {beta}3 Nicotinic Receptor Subunit: A Component of {alpha}-Conotoxin MII-Binding Nicotinic Acetylcholine Receptors that Modulate Dopamine Release and Related Behaviors
J. Neurosci., December 3, 2003; 23(35): 11045 - 11053.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
M. Quik, T. Bordia, M. Okihara, H. Fan, M. J. Marks, J. M. McIntosh, and P. Whiteaker
L-DOPA Treatment Modulates Nicotinic Receptors in Monkey Striatum
Mol. Pharmacol., September 1, 2003; 64(3): 619 - 628.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2003 by the American Society for Pharmacology and Experimental Therapeutics