![[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}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
NEUROPHARMACOLOGY
Department of Pharmacology, George Washington University Medical Center, Washington, District of Columbia
Subtypes of neuronal nicotinic acetylcholine receptors (nAChRs) are differentially sensitive to up-regulation by chronic nicotine exposure in vitro. To determine whether this occurs in animals, rats were implanted with minipumps containing saline ± nicotine (6.0 mg/kg/rat/day) for 14 days. Autoradiography with [125I]epibatidine using 3-(2(S)-azetidinylmethoxy)pyridine dihydrochloride (A-85380) or cytisine as selective competitors allowed quantitative measurement in 33 regions of 3 families of nAChR binding, with properties of 
4
2, 34, and 3/62. Chronic nicotine exposure caused increases of 20 to 100% for 42-like binding in most regions surveyed. However, binding to this subtype was not increased in some regions, including habenulopeduncular structures, certain thalamic nuclei, and several brainstem regions. In 9 of 33 regions, including catecholaminergic areas and visual structures, 3/62-like binding represented >10% of total binding. Binding to this subtype was up-regulated by nicotine in only two of these nine regions: the nucleus accumbens and superior colliculus. 34-Like binding represented >10% of total in 15 of the 33 regions surveyed. Binding to this subtype was increased by nicotine in only 1 of these 15 regions, and actually decreased in subiculum and cerebellum. These studies yielded two principal findings. First, chronic nicotine exposure selectively up-regulates 42-like binding, with relatively little effect on 3/62-like and 34-like binding in vivo. Second, up-regulation by chronic nicotine exposure shows considerable regional variation. Differential subtype sensitivity to chronic nicotine exposure may contribute to altered pharmacological response in individuals who smoke or use nicotine replacement therapy.
Address correspondence to: Dr. David C. Perry, Department of Pharmacology, George Washington University Medical Center, 2300 I Street N.W., Washington, DC 20037. E-mail: phmdcp{at}gwumc.edu
This article has been cited by other articles:
|
|
 |
|
  C. Xiao, R. Nashmi, S. McKinney, H. Cai, J. M. McIntosh, and H. A. Lester Chronic Nicotine Selectively Enhances {alpha}4{beta}2* Nicotinic Acetylcholine Receptors in the Nigrostriatal Dopamine Pathway J. Neurosci., October 7, 2009; 29(40): 12428 - 12439. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Coddou, E. Bravo, and J. Eugenin Alterations in cholinergic sensitivity of respiratory neurons induced by pre-natal nicotine: a mechanism for respiratory dysfunction in neonatal mice Phil Trans R Soc B, September 12, 2009; 364(1529): 2527 - 2535. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. P. Cosgrove, J. Batis, F. Bois, P. K. Maciejewski, I. Esterlis, T. Kloczynski, S. Stiklus, S. Krishnan-Sarin, S. O'Malley, E. Perry, et al. {beta}2-Nicotinic Acetylcholine Receptor Availability During Acute and Prolonged Abstinence From Tobacco Smoking Arch Gen Psychiatry, June 1, 2009; 66(6): 666 - 676. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. D. Buckingham, A. K. Jones, L. A. Brown, and D. B. Sattelle Nicotinic Acetylcholine Receptor Signalling: Roles in Alzheimer's Disease and Amyloid Neuroprotection Pharmacol. Rev., March 1, 2009; 61(1): 39 - 61. [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]
|
|
|
|
|
|
J. K. Staley, S. Krishnan-Sarin, K. P. Cosgrove, E. Krantzler, E. Frohlich, E. Perry, J. A. Dubin, K. Estok, E. Brenner, R. M. Baldwin, et al. Human Tobacco Smokers in Early Abstinence Have Higher Levels of beta2* Nicotinic Acetylcholine Receptors than Nonsmokers. J. Neurosci., August 23, 2006; 26(34): 8707 - 8714. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Picard, D. Bruel, D. Servent, W. Saba, C. Fruchart-Gaillard, M.-A. Schollhorn-Peyronneau, D. Roumenov, E. Brodtkorb, S. Zuberi, A. Gambardella, et al. Alteration of the in vivo nicotinic receptor density in ADNFLE patients: a PET study Brain, August 1, 2006; 129(8): 2047 - 2060. [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]
|
|
|
|
|
|
C. Unger, M. M. Svedberg, W.-F. Yu, M. M. Hedberg, and A. Nordberg Effect of Subchronic Treatment of Memantine, Galantamine, and Nicotine in the Brain of Tg2576 (APPswe) Transgenic Mice J. Pharmacol. Exp. Ther., April 1, 2006; 317(1): 30 - 36. [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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
R. Salas, F. Pieri, and M. De Biasi Decreased Signs of Nicotine Withdrawal in Mice Null for the {beta}4 Nicotinic Acetylcholine Receptor Subunit J. Neurosci., November 10, 2004; 24(45): 10035 - 10039. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Buccafusco Neuronal Nicotinic Receptor Subtypes: DEFINING THERAPEUTIC TARGETS Mol. Interv., October 1, 2004; 4(5): 285 - 295. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Sallette, S. Bohler, P. Benoit, M. Soudant, S. Pons, N. Le Novere, J.-P. Changeux, and P. J. Corringer An Extracellular Protein Microdomain Controls Up-regulation of Neuronal Nicotinic Acetylcholine Receptors by Nicotine J. Biol. Chem., April 30, 2004; 279(18): 18767 - 18775. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
