Nicotinic α5 subunit deletion locally reduces high‐affinity agonist activation without altering nicotinic receptor numbers
Abstract
Neuronal nicotinic acetylcholine receptor subunit α5 mRNA is widely expressed in the CNS. An α5 gene polymorphism has been implicated in behavioral differences between mouse strains, and α5‐null mutation induces profound changes in mouse acute responses to nicotine. In this study, we have examined the distribution and prevalence of α5* nicotinic acetylcholine receptor in mouse brain, and quantified the effects of α5‐null mutation on pre‐synaptic nicotinic acetylcholine receptor function (measured using synaptosomal 86 Rb+efflux) and overall [125 I]epibatidine binding site expression. α5* nicotinic acetylcholine receptor expression was found in nine of fifteen regions examined, although < 20% of the total nicotinic acetylcholine receptor population in any region contained α5. Deletion of the α5 subunit gene resulted in localized loss of function (thalamus, striatum), which was itself confined to the DHβE‐sensitive receptor population. No changes in receptor expression were seen. Consequently, functional changes must occur as a result of altered function per unit of receptor. The selective depletion of high agonist activation affinity sites results in overall nicotinic function being reduced, and increases the overall agonist activation affinity. Together, these results describe the receptor‐level changes underlying altered behavioral responses to nicotine in nicotinic acetylcholine receptor α5 subunit‐null mutants.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In rodent brain, the α5 subunit is found in some but not all α4β2* receptors in cortex, thalamus, striatum, hippocampus, medial habenula, olfactory tubercle, hypothalamus, and midbrain (dopaminergic neurons only).
“In rodent brain which has been extensively studied, it is found in some, but not all, α4β2* receptors in cortex, thalamus, striatum, hippocampus, medial habenula, olfactory tubercle, hypothalamus, and midbrain (dopaminergic neurons only) (105,106).”
From Nicotine is a selective pharmacological chaperone of acetylcholine receptor number and stoichiometry. Implications for drug discovery (2009) · cites this paper as [105]
Cites
PROTEIN MEASUREMENT WITH THE FOLIN PHENOL REAGENT
Lowry, O. H., Rosebrough, N., Farr, A. L., & Randall, R. (1951) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)52451-6 · Cited by 315,771 · see citing works
Gray, E. G., & Whittaker, V. P. (1962) · PubMed · Cited by 2,530 · see citing works
Presynaptic nicotinic ACh receptors
Wonnacott, S. (1997) · Trends in Neurosciences · doi:10.1016/s0166-2236(96)10073-4 · Cited by 1,308 · see citing works
Neuronal nicotinic receptors: from structure to pathology
Gotti, C., & Clementi, F. (2004) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2004.09.006 · Cited by 970 · see citing works
The origins of cholinergic and other subcortical afferents to the thalamus in the rat
Hallanger, A. E., Levey, A. I., Lee, H. J., Rye, D. B., & Wainer, B. H. (1987) · The Journal of Comparative Neurology · doi:10.1002/cne.902620109 · Cited by 595 · see citing works
Nicotine binding and nicotinic receptor subunit RNA after chronic nicotine treatment
Marks, M., Pauly, Jr., Gross, S., Deneris, E., Hermans-Borgmeyer, I., Heinemann, S., & Collins, A. (1992) · The Journal of Neuroscience · doi:10.1523/jneurosci.12-07-02765.1992 · Cited by 551 · see citing works
Self-citationAlkondon, M., & Albuquerque, E. X. (1993) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)38283-2 · Cited by 538 · see citing works
Champtiaux, N., Gotti, C., Cordero‐Erausquin, M., David, D. J. P., Przybylski, C., Léna, C., Clementi, F., Moretti, M., Rossi, F., Novère, N. G. L., et al. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-21-07820.2003 · Cited by 505 · see citing works
Salminen, O., Murphy, K. L., McIntosh, J. M., Drago, J., Marks, M. J., Collins, A. C., & Grady, S. R. (2004) · Molecular Pharmacology · doi:10.1124/mol.65.6.1526 · Cited by 401 · see citing works
Self-citationFunctional contributions of α5 subunit to neuronal acetylcholine receptor channels
Ramírez-Latorre, J. A., Yu, C., Qu, X., Perin, F., Karlin, A., & Role, L. W. (1996) · Nature · doi:10.1038/380347a0 · Cited by 397 · see citing works
Assembly of Human Neuronal Nicotinic Receptor α5 Subunits with α3, β2, and β4 Subunits
Wang, F., Gerzanich, V., Wells, G. B., Anand, R., Peng, X.-D., Keyser, K. T., & Lindstrom, J. M. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.30.17656 · Cited by 345 · see citing works
Self-citationVernallis, A. B., Conroy, W. G., & Berg, D. K. (1993) · Neuron · doi:10.1016/0896-6273(93)90333-m · Cited by 304 · see citing works
Boulter, J., O'Shea-Greenfield, A., Duvoisin, R. M., Connolly, J. G., Wada, E., Jensen, A., Gardner, P. D., Ballivet, M., Deneris, E. S., & McKinnon, D. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)39588-2 · Cited by 302 · see citing works
Wada, E., McKinnon, D. H., Heinemann, S., Patrick, J., & Swanson, L. W. (1990) · Brain Research · doi:10.1016/0006-8993(90)90248-a · Cited by 254 · see citing works
Gerzanich, V., Wang, F., Kuryatov, A., & Lindstrom, J. M. (1998) · PubMed · Cited by 242 · see citing works
Self-citationKuryatov, A., Gerzanich, V., Nelson, M. E., Olale, F., & Lindstrom, J. M. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-23-09035.1997 · Cited by 227 · see citing works
Self-citationHuman α6 AChR subtypes: subunit composition, assembly, and pharmacological responses
Kuryatov, A., Olale, F., Cooper, J., Choi, C. H., & Lindstrom, J. M. (2000) · Neuropharmacology · doi:10.1016/s0028-3908(00)00144-1 · Cited by 223 · see citing works
Self-citationTiseo, P. J., & Inturrisi, C. E. (1993) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)10118-3 · Cited by 216 · see citing works
Zwart, R., & Vijverberg, H. P. M. (1998) · Molecular Pharmacology · doi:10.1124/mol.54.6.1124 · Cited by 215 · see citing works
Chen, D., & Patrick, J. W. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.38.24024 · Cited by 206 · see citing works
The Nicotinic Acetylcholine Receptor Subunit α5 Mediates Short-Term Effects of Nicotine in Vivo
Salas, R., Orr‐Urtreger, A., Broide, R. S., Beaudet, A. L., Paylor, R. E., & Biasi, M. D. (2003) · Molecular Pharmacology · doi:10.1124/mol.63.5.1059 · Cited by 200 · see citing works
Tapia, L., Kuryatov, A., & Lindstrom, J. M. (2006) · Molecular Pharmacology · doi:10.1124/mol.106.030445 · Cited by 196 · see citing works
Self-citationCouturier, S., Erkman, L., Valera, S., Rungger, D., Bertrand, S., Boulter, J., Ballivet, M., & Bertrand, D. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)38201-2 · Cited by 190 · see citing works
Wang, F., Nelson, M. E., Kuryatov, A., Olale, F., Cooper, J., Keyser, K., & Lindstrom, J. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.44.28721 · Cited by 187 · see citing works
Self-citationNicotinic Acetylcholine Receptors of Muscles and Nerves
Lindstrom, J. M. (2003) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1254.007 · Cited by 176 · see citing works
Self-citationHuman α4β2 Acetylcholine Receptors Formed from Linked Subunits
Zhou, Y., Nelson, M. E., Kuryatov, A., Choi, C., Cooper, J., & Lindstrom, J. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-27-09004.2003 · Cited by 174 · see citing works
Self-citation5-Iodo-A-85380, an α4β2 Subtype-Selective Ligand for Nicotinic Acetylcholine Receptors
Mukhin, A. G., Gündisch, D., Horti, A. G., Koren, A. O., Tamagnan, G., Kimes, A. S., Chambers, J., Vaupel, D. B., King, S. L., Picciotto, M. R., et al. (2000) · Molecular Pharmacology · doi:10.1124/mol.57.3.642 · Cited by 173 · see citing works
125I-α-Conotoxin MII Identifies a Novel Nicotinic Acetylcholine Receptor Population in Mouse Brain
Whiteaker, P., McIntosh, J. M., Luo, S., Collins, A. C., & Marks, M. J. (2000) · Molecular Pharmacology · doi:10.1016/s0026-895x(24)26500-7 · Cited by 160 · see citing works
Self-citationWhiteaker, P., McIntosh, J. M., Luo, S., Collins, A. C., & Marks, M. J. (2000) · PubMed · Cited by 158 · see citing works
Self-citationMiwa, J. M., Stevens, T. R., King, S. L., Caldarone, B. J., Ibanez-Tallon, I., Xiao, C., Fitzsimonds, R. M., Pavlides, C., Lester, H. A., Picciotto, M. R., et al. (2006) · Neuron · doi:10.1016/j.neuron.2006.07.025 · Cited by 154 · see citing works
Differential Agonist Inhibition Identifies Multiple Epibatidine Binding Sites in Mouse Brain
Marks, M. J., Smith, K. W., & Collins, A. C. (1998) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)37384-7 · Cited by 140 · see citing works
Self-citationGotti, C., Moretti, M., Clementi, F., Riganti, L., McIntosh, J. M., Collins, A. C., Marks, M. J., & Whiteaker, P. (2005) · Molecular Pharmacology · doi:10.1124/mol.105.011940 · Cited by 133 · see citing works
Self-citationGerzanich, V., Wang, F., Kuryatov, A., & Lindstrom, J. M. (1998) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)37589-5 · Cited by 129 · see citing works
Self-citationMarks, M. J., Whiteaker, P., Calcaterra, J., Stitzel, J. A., Bullock, A. E., Grady, S. R., Picciotto, M. R., Changeux, J., & Collins, A. C. (1999) · PubMed · Cited by 126 · see citing works
Self-citationMarks, M. J., Farnham, D. A., Grady, S. R., & Collins, A. C. (1993) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)10175-4 · Cited by 112 · see citing works
Self-citationIdentification of a novel nicotinic binding site in mouse brain using [125I]‐epibatidine
Whiteaker, P., Jimenez, M., McIntosh, J. M., Collins, A. C., & Marks, M. J. (2000) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0703616 · Cited by 105 · see citing works
Self-citationSargent, P. B., Pike, S., Nadel, D., & Lindström, J. (1989) · Journal of Neuroscience · doi:10.1523/jneurosci.09-02-00565.1989 · Cited by 92 · see citing works
Kedmi, M., Beaudet, A. L., & Orr‐Urtreger, A. (2004) · Physiological Genomics · doi:10.1152/physiolgenomics.00202.2003 · Cited by 89 · see citing works
King, S. L., Marks, M. J., Grady, S. R., Caldarone, B. J., Koren, A. O., Mukhin, A. G., Collins, A. C., & Picciotto, M. R. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-09-03837.2003 · Cited by 82 · see citing works
Self-citationGirod, R., Crabtree, G. W., Ernstrom, G. G., Ramírez-Latorre, J. A., McGehee, D. S., Turner, J. R., & Role, L. W. (1999) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1999.tb11331.x · Cited by 81 · see citing works
Autonomic function in mice lacking α5 neuronal nicotinic acetylcholine receptor subunit
Wang, N., Orr‐Urtreger, A., Chapman, J., Rabinowitz, R., Nachman, R., & Korczyn, A. D. (2002) · The Journal of Physiology · doi:10.1113/jphysiol.2001.013456 · Cited by 79 · see citing works
Winzer‐Serhan, U. H., & Leslie, F. M. (2004) · The Journal of Comparative Neurology · doi:10.1002/cne.20357 · Cited by 79 · see citing works
Marks, M. J., Whiteaker, P., Calcaterra, J., Stitzel, J. A., Bullock, A. E., Grady, S. R., Picciotto, M. R., Changeux, J.-P., & Collins, A. C. (1999) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)38240-0 · Cited by 79 · see citing works
Self-citationTumkosit, P., Kuryatov, A., Luo, J., & Lindstrom, J. (2006) · Molecular Pharmacology · doi:10.1124/mol.106.027326 · Cited by 73 · see citing works
Self-citation(2000) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-57079-7 · Cited by 72 · see citing works
Gotti, C., Moretti, M., Zanardi, A., Gaimarri, A., Champtiaux, N., Changeux, J., Whiteaker, P., Marks, M. J., Clementi, F., & Zoli, M. (2005) · Molecular Pharmacology · doi:10.1124/mol.105.015925 · Cited by 71 · see citing works
Self-citationGroot‐Kormelink, P. J., Boorman, J. P., & Sivilotti, L. G. (2001) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0704313 · Cited by 64 · see citing works
Smit, A. B., Brejc, K., Syed, N. I., & Sixma, T. K. (2003) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1254.010 · Cited by 61 · see citing works
Neuronal and Extraneuronal Expression and Regulation of the Human α5 Nicotinic Receptor Subunit Gene
Flora, A., Schulz, R., Benfante, R., Battaglioli, E., Terzano, S., Clementi, F., & Fornasari, D. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.0750018.x · Cited by 47 · see citing works
Stitzel, J. A., Blanchette, J., & Collins, A. C. (1998) · PubMed · Cited by 46 · see citing works
Self-citationNicotinic acetylcholine receptor α5 subunits modulate oxotremorine-induced salivation and tremor
Wang, N., Orr‐Urtreger, A., Chapman, J., Rabinowitz, R., & Korczyn, A. D. (2004) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2004.04.009 · Cited by 9 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Habenular α5 nicotinic receptor subunit signalling controls nicotine intake
Fowler, C. D., Lu, Q., Johnson, P. M., Marks, M. J., & Kenny, P. J. (2011) · Nature · doi:10.1038/nature09797 · Cited by 663 · see citing works
Structural and functional diversity of native brain neuronal nicotinic receptors
Gotti, C., Clementi, F., Fornari, A., Gaimarri, A., Guiducci, S., Manfredi, I., Moretti, M., Pedrazzi, P., Pucci, L., & Zoli, M. (2009) · Biochemical Pharmacology · doi:10.1016/j.bcp.2009.05.024 · Cited by 469 · see citing works
Diversity of vertebrate nicotinic acetylcholine receptors
Millar, N. S., & Gotti, C. (2009) · Neuropharmacology · doi:10.1016/j.neuropharm.2008.07.041 · Cited by 441 · see citing works
“For example, amongst a4b2* nAChRs (a subtype which is very widely distributed within the brain), approximately 20% of these receptors also contain the a5 subunit (Brown et al., 2007).”
BackgroundWeiss, R. B., Baker, T. B., Cannon, D. S., von Niederhausern, A., Dunn, D. M., Matsunami, N., Singh, N. A., Baird, L., Coon, H., McMahon, W. M., et al. (2008) · PLoS Genetics · doi:10.1371/journal.pgen.1000125 · Cited by 271 · see citing works
The subtypes of nicotinic acetylcholine receptors on dopaminergic terminals of mouse striatum
Grady, S. R., Salminen, O., Laverty, D. C., Whiteaker, P., McIntosh, J. M., Collins, A. C., & Marks, M. J. (2007) · Biochemical Pharmacology · doi:10.1016/j.bcp.2007.07.032 · Cited by 252 · see citing works
Self-citationRoles of Accessory Subunits in α4β2* Nicotinic Receptors
Kuryatov, A., Onksen, J., & Lindstrom, J. (2008) · Molecular Pharmacology · doi:10.1124/mol.108.046789 · Cited by 195 · see citing works
Self-citationWang, J. C. C., Cruchaga, C., Saccone, N. L., Bertelsen, S. E., Liu, P., Budde, J., Duan, W., Fox, L. W., Grucza, R. A., Kern, J., et al. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp231 · Cited by 187 · see citing works
Kuryatov, A., Berrettini, W., & Lindstrom, J. (2011) · Molecular Pharmacology · doi:10.1124/mol.110.066357 · Cited by 171 · see citing works
“Their high sensitivity to activation by nicotine and high Ca2 permeability give them substantial functional impact (Brown et al., 2007; Tapia et al., 2007; Kuryatov et al., 2008; Grady et al., 2010).”
BackgroundSelf-citationLester, H. A., Xiao, C., Srinivasan, R., Son, C. D., Miwa, J., Pantoja, R., Banghart, M. R., Dougherty, D. A., Goate, A. M., & Wang, J. C. (2009) · The AAPS Journal · doi:10.1208/s12248-009-9090-7 · Cited by 163 · see citing works
“In rodent brain which has been extensively studied, it is found in some, but not all, α4β2* receptors in cortex, thalamus, striatum, hippocampus, medial habenula, olfactory tubercle, hypothalamus, and midbrain (dopaminergic neurons only) (105,106).”
BackgroundJackson, K. J., Marks, M. J., Vann, R. E., Chen, X., Gamage, T. F., Warner, J. A., & Damaj, M. I. (2010) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.110.165738 · Cited by 156 · see citing works
“Acetylcholine-stimulated 86Rb efflux from synaptosomes was investigated using the published methods of Marks et al. (1999, 2007) and Brown et al. (2007), with minor modifications.”
BackgroundMethodResultThe Nicotinic Acetylcholine Receptor 5 Subunit Plays a Key Role in Attention Circuitry and Accuracy
Bailey, C. D. C., De Biasi, M., Fletcher, P. J., & Lambe, E. K. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.2258-10.2010 · Cited by 146 · see citing works
“…contrasts greatly with immunoprecipitation analyses suggesting that only 14 –16% of 4 2* nAChRs in the whole cerebral cortex contain the 5 subunit (Brown et al., 2007; Mao et al., 2008), suggesting that layer VI neurons contain a disproportionate level of the unusual 4 2 5 subtype of nicotinic…”
BackgroundDrenan, R. M., Grady, S. R., Steele, A. D., McKinney, S., Patzlaff, N. E., McIntosh, J. M., Marks, M. J., Miwa, J. M., & Lester, H. A. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.2056-10.2010 · Cited by 127 · see citing works
“Previously published methods (Marks et al., 2006; Brown et al., 2007) were followed to measure high-affinity [ 125I]epibatidine (2200 Ci/ mmol) binding to membrane preparations using a 96-well plate format.”
MethodDevelopmental Excitation of Corticothalamic Neurons by Nicotinic Acetylcholine Receptors
Kassam, S. M., Herman, P. M., Goodfellow, N. M., Alves, N. C., & Lambe, E. K. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.2645-08.2008 · Cited by 100 · see citing works
“Inclusion of the 5 accessory subunit is also thought to alter several parameters of 4 2* nicotinic receptors (Brown et al., 2007; Tapia et al., 2007; Kuryatov et al., 2008).”
BackgroundInside-out neuropharmacology of nicotinic drugs
Henderson, B. J., & Lester, H. A. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.01.022 · Cited by 102 · see citing works
“These various AChR subtypes exhibit a diverse range of sensitivities to nicotine and other nicotinic ligands (Albuquerque et al., 2009; Brown et al., 2007; Chavez-Noriega et al., 1997; Jensen et al., 2005; Kuryatov and Lindstrom, 2011; Tapia et al., 2007).”
An autoradiographic survey of mouse brain nicotinic acetylcholine receptors defined by null mutants
Baddick, C. G., & Marks, M. J. (2011) · Biochemical Pharmacology · doi:10.1016/j.bcp.2011.04.019 · Cited by 75 · see citing works
“Nevertheless, no study, including the current one, has been able to detect a change in the total number epibatidine binding sites [36, 48], despite the significant changes in function, pharmacology and physiology resulting from α5 gene deletion [48, 51, 89].”
BackgroundMcClure‐Begley, T. D., King, N. M., Collins, A. C., Stitzel, J. A., Wehner, J. M., & Butt, C. M. (2009) · Molecular Pharmacology · doi:10.1124/mol.108.052274 · Cited by 72 · see citing works
“Indeed, previous studies performed in our laboratory (Brown et al., 2007) showed that deletion of the 5 subunit decreased maximal agonist-evoked 86Rb efflux in several brain reThis work was supported by the National Institutes of Health National Institute on Alcohol Abuse and Alcoholism [Grants…”
BackgroundInfluentialSelf-citationMarks, M. J., McClure-Begley, T. D., Whiteaker, P., Salminen, O., Brown, R. W. B., Cooper, J., Collins, A. C., & Lindstrom, J. M. (2011) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.110.178236 · Cited by 70 · see citing works
“Subsequently, [125I]epibatidine, the binding of which is unaffected by Triton X-100 solubilization, was used to measure nAChR binding sites in the immunoprecipitation studies using a modification of a previously published method (Brown et al., 2007).”
MethodSelf-citationBailey, C. D. C., Alves, N. C., Nashmi, R., De Biasi, M., & Lambe, E. K. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.09.011 · Cited by 69 · see citing works
Gotti, C., Moretti, M., Meinerz, N. M., Clementi, F., Gaimarri, A., Collins, A. C., & Marks, M. J. (2008) · Molecular Pharmacology · doi:10.1124/mol.108.045203 · Cited by 68 · see citing works
“We chose cortex and thalamus for the studies reported here because gene deletion experiments showed that almost all [3H]epibatidine binding sites (Marks et al., 2006, 2007) and 86Rb efflux (Marks et al., 2000, 2007) in these brain regions are 4 2, with a small fraction of 4 5 2 (Brown et al., 2007).”
BackgroundMethodResultSelf-citationNicotinic modulation of hippocampal cell signaling and associated effects on learning and memory
Kutlu, M. G., & Gould, T. J. (2015) · Physiology & Behavior · doi:10.1016/j.physbeh.2015.12.008 · Cited by 62 · see citing works
“In the hippocampus, the predominant nAChR subtypes are α7 nAChRs and α4β2 nAChRs [8, 9]; though there is also a high density of α5 subunits [10], which can combine to form α4β2α5 nAChRs.”
BackgroundGrady, S. R., Salminen, O., McIntosh, J. M., Marks, M. J., & Collins, A. C. (2009) · Journal of Molecular Neuroscience · doi:10.1007/s12031-009-9263-y · Cited by 61 · see citing works
“epibatidine binding ( Brown et al. 2007 ) that absolutely requires α4 and β2 subunits (Marks et al. 2007), or in [ 125 ]”
InfluentialSelf-citationMolecular mechanisms for nicotine intoxication
Alkam, T., & Nabeshima, T. (2019) · Neurochemistry International · doi:10.1016/j.neuint.2019.02.006 · Cited by 62 · see citing works
Bağdaş, D., AlSharari, S. D., Freitas, K., Tracy, M. E., & Damaj, M. I. (2015) · Biochemical Pharmacology · doi:10.1016/j.bcp.2015.04.013 · Cited by 61 · see citing works
Proulx, É., Piva, M., Tian, M. K., Bailey, C. D. C., & Lambe, E. K. (2013) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-013-1481-3 · Cited by 57 · see citing works
Heath, C. J., King, S. L., Gotti, C., Marks, M. J., & Picciotto, M. R. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2010.130 · Cited by 59 · see citing works
“7A), consistent with the expression of nAChR subtypes activated by relatively low ACh concentrations (Brown et al , 2007; Gotti et al , 2008; Marks et al , 2007) including the ( α 4) 2 ( β 2) 3 and ( α 4) 2 ( β 2) 2 α 5 nAChR subtypes, in corticothalamic projection neurons.”
InfluentialFunction of Human α3β4α5 Nicotinic Acetylcholine Receptors Is Reduced by the α5(D398N) Variant
George, A. A., Lucero, L. M., Damaj, M. I., Lukas, R. J., Chen, X., & Whiteaker, P. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.379339 · Cited by 58 · see citing works
Self-citationGrady, S. R., Wageman, C. R., Patzlaff, N. E., & Marks, M. J. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.12.026 · Cited by 56 · see citing works
“…the (a4b2)2a5-nAChR has also been demonstrated in mouse brain by 86Rbþ efflux experiments using synaptosomal preparations from striatum and thalamus (Brown et al., 2007) and in a transgenic mouse in cortico-thalamic terminals (Heath et al., 2010), as well as by [3H]-GABA release in cortex…”
BackgroundA Review of the Cholinergic System and Therapeutic Approaches to Treat Brain Disorders
Bertrand, D., & Wallace, T. L. (2020) · Current topics in behavioral neurosciences · doi:10.1007/7854_2020_141 · Cited by 54 · see citing works
Grupe, M., Grunnet, M., Bastlund, J. F., & Jensen, A. A. (2014) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/bcpt.12361 · Cited by 54 · see citing works
Nicotinic acetylcholine receptors and epilepsy
Becchetti, A., Grandi, L. C., Cerina, M., & Amadeo, A. (2023) · Pharmacological Research · doi:10.1016/j.phrs.2023.106698 · Cited by 53 · see citing works
Chen, L.-S., Baker, T. B., Jorenby, D. E., Piper, M. E., Saccone, N. L., Johnson, E. O., Breslau, N., Hatsukami, D. K., Carney, R. M., & Bierut, L. J. (2015) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2015.06.022 · Cited by 40 · see citing works
“Further studies have demonstrated change in the receptor function in response to nicotine agonists given this amino acid change in the a5 nicotinic receptor subunit (Bierut et al., 2008a; Brown et al., 2007).”
BackgroundPerez, X. A., O’Leary, K. T., Parameswaran, N., McIntosh, J. M., & Quik, M. (2009) · Molecular Pharmacology · doi:10.1124/mol.108.053801 · Cited by 38 · see citing works
“…the primary regulators of striatal dopamine release, there is also evidence for heterogeneity in 4 2* nAChRs in monkey putamen, including the expression of 4 2 and 4 5 2 nAChRs (Quik et al., 2005), which exhibit differential functional characteristics (Brown et al., 2007; Kuryatov et al., 2008).”
BackgroundChatterjee, S., Santos, N., Holgate, J. Y., Haass‐Koffler, C. L., Hopf, F. W., Kharazia, V., Lester, H. A., Bonci, A., & Bartlett, S. E. (2013) · PLoS ONE · doi:10.1371/journal.pone.0068300 · Cited by 39 · see citing works
“The α5-/- mice were found to have normal transcript levels for all nAChRs subunits, including α4 and β2 in all brain areas including the VTA [35,50].”
BackgroundCurrent Progress on Central Cholinergic Receptors as Therapeutic Targets for Alzheimer's Disease
Nagori, K., Pradhan, M., Sharma, M. K., Ajazuddin, M., Badwaik, H. R., & Nakhate, K. T. (2024) · Current Alzheimer Research · doi:10.2174/0115672050306008240321034006 · Cited by 37 · see citing works
Neurochemical organization of the ventral striatum’s olfactory tubercle
Cansler, H. L., Wright, K. N., Stetzik, L. A., & Wesson, D. W. (2019) · Journal of Neurochemistry · doi:10.1111/jnc.14919 · Cited by 34 · see citing works
Hone, A. J., McIntosh, J. M., Azam, L., Lindstrom, J. M., Lucero, L. M., Whiteaker, P., Passas, J., Blázquez, J., & Albillos, A. (2015) · Molecular Pharmacology · doi:10.1124/mol.115.100982 · Cited by 34 · see citing works
Self-citationMarks, M. J., Meinerz, N. M., Brown, R. W. B., & Collins, A. C. (2010) · Biochemical Pharmacology · doi:10.1016/j.bcp.2010.06.040 · Cited by 33 · see citing works
“Changes in the relative proportion of high sensitivity (HS) and low sensitivity (LS) components observed for mice heterozygotic for α4 or β2 gene expression are consistent with the hypothesis that these components reflect the activity of receptors with different α/β stoichiometries [15], although the α5 subunit contri…”
BackgroundSelf-citationThe α5 Nicotinic Acetylcholine Receptor Subunit Differentially Modulates α4β2* and α3β4* Receptors
Scholze, P., & Huck, S. (2020) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2020.607959 · Cited by 31 · see citing works
“…the MHb, IPN, hippocampus, striatum, thalamus, prefrontal cortex (PFC), substantia nigra, ventral tegmental area (VTA), brainstem, and spinal cord (Brown et al., 2007; Counotte Frontiers in Synaptic Neuroscience | www.frontiersin.org 3 December 2020 | Volume 12 | Article 607959 S c h o lze…”
BackgroundMethodInfluentialJohn Daly’s Compound, Epibatidine, Facilitates Identification of Nicotinic Receptor Subtypes
Marks, M. J., Laverty, D. C., Whiteaker, P., Salminen, O., Grady, S. R., McIntosh, J. M., & Collins, A. C. (2009) · Journal of Molecular Neuroscience · doi:10.1007/s12031-009-9264-x · Cited by 32 · see citing works
“Furthermore, gene deletion and immunoprecipitation establish that some of these sites also contain the α5 subunit (Brown et al. 2007).”
Self-citationSelectivity of ABT-089 for α4β2* and α6β2* nicotinic acetylcholine receptors in brain
Marks, M. J., Wageman, C. R., Grady, S. R., Gopalakrishnan, M., & Briggs, C. A. (2009) · Biochemical Pharmacology · doi:10.1016/j.bcp.2009.05.022 · Cited by 30 · see citing works
“Indeed, it has previously been reported that deletion of the α5 subunit elicited a larger decrease in efflux in thalamus than in the other regions [5], suggesting that ABT-089 may act through α4α5β2-nAChR selectively compared to α4β2 nAChR.”
InfluentialJain, A., Kuryatov, A., Wang, J., Kamenecka, T. M., & Lindstrom, J. M. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.749150 · Cited by 31 · see citing works
Self-citationThe Road to Discovery of Neuronal Nicotinic Cholinergic Receptor Subtypes
Collins, A. C., Salminen, O., Marks, M. J., Whiteaker, P., & Grady, S. R. (2009) · Handbook of experimental pharmacology · doi:10.1007/978-3-540-69248-5_4 · Cited by 30 · see citing works
“Deletion of the α7, β4 (Marks et al. 2006), and α5 (Brown et al. 2007) subunits does not produce a detectable change in cytisine-sensitive higher affinity [3H]-epibatidine binding.”
BackgroundSelf-citationWhiteaker, P., Wilking, J. A., Brown, R. W. B., Brennan, R. J., Collins, A. C., Lindstrom, J. M., & Boulter, J. (2009) · Acta Pharmacologica Sinica · doi:10.1038/aps.2009.68 · Cited by 28 · see citing works
Self-citationJin, X., Bermúdez, I., & Steinbach, J. H. (2013) · Molecular Pharmacology · doi:10.1124/mol.113.089979 · Cited by 28 · see citing works
“It has been proposed that the a5 subunit, in particular, cannot incorporate into a functional receptor in a position at which it contributes to a canonical binding site (Brown et al., 2007; Kuryatov et al., 2008).”
BackgroundButt, C. M., Alptekin, A., Shippenberg, T. S., & Öz, M. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05225.x · Cited by 29 · see citing works
Liu, W., & Li, M. D. (2017) · Current Neuropharmacology · doi:10.2174/1570159x15666170801103009 · Cited by 27 · see citing works
Zhang, J., Xiao, Y.-D., Green-Jordan, K., Hammond, P. S., Dyke, K. M. V., Mazurov, A. A., Speake, J. D., Lippiello, P. M., James, J. W., Letchworth, S. R., et al. (2012) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2012.09.014 · Cited by 26 · see citing works
Li, P., McCollum, M. M., Bracamontes, J. R., Steinbach, J. H., & Akk, G. (2011) · Molecular Pharmacology · doi:10.1124/mol.111.073841 · Cited by 25 · see citing works
Toma, W. B., Ulker, E., Alqasem, M., AlSharari, S. D., McIntosh, J. M., & Damaj, M. I. (2020) · Current topics in behavioral neurosciences · doi:10.1007/7854_2020_135 · Cited by 25 · see citing works
Dawson, A., Wolstenholme, J. T., Roni, M. A., Campbell, V. C., Jackson, A. B., Slater, C. A., Bağdaş, D., Perez, E. E., Bettinger, J. C., Biasi, M. D., et al. (2018) · Neuropharmacology · doi:10.1016/j.neuropharm.2018.06.031 · Cited by 24 · see citing works
“Although high levels of expression are found only in few brain areas (Salas et al., 2003a), Chrna5 mRNA has been found in themajority of brain regions (Brown et al., 2007), suggesting that a5* nAChRs could have a substantial impact on brain function.”
BackgroundNichols, W. A., Henderson, B. J., Marotta, C. B., Yu, C., Richards, C. I., Dougherty, D. A., Lester, H. A., & Cohen, B. N. (2016) · PLoS ONE · doi:10.1371/journal.pone.0158032 · Cited by 23 · see citing works
“The α4 and β2 nicotinic subunits also co-assemble with α5 in the brain to form α5α4β2 nAChRs [25].”
Beiranvand, F., Zlabinger, C., Orr‐Urtreger, A., Ristl, R., Huck, S., & Scholze, P. (2014) · British Journal of Pharmacology · doi:10.1111/bph.12841 · Cited by 22 · see citing works
Hoegberg, B. G., Lomazzo, E., Lee, N. H., & Perry, D. C. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.08.015 · Cited by 17 · see citing works
“These nAChRs are highly sensitive to activation by nicotine (Brown et al., 2007) and are also highly Ca2+ Hoegberg et al.”
BackgroundChrna4 A529 knock-in mice exhibit altered nicotine sensitivity
Wilking, J. A., Hesterberg, K. G., Crouch, E. L., Homanics, G. E., & Stitzel, J. A. (2010) · Pharmacogenetics and Genomics · doi:10.1097/fpc.0b013e3283369347 · Cited by 20 · see citing works
The Hair Cell α9α10 Nicotinic Acetylcholine Receptor: Odd Cousin in an Old Family
Lipovsek, M., Marcovich, I., & Elgoyhen, A. B. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.785265 · Cited by 19 · see citing works
Low-Dose Nicotine Activates EGFR Signaling via α5-nAChR and Promotes Lung Adenocarcinoma Progression
Wang, M., Hsu, Y.-F., Liu, C.-H., Kuo, Y.-L., Chen, Y., Yeh, Y., Ho, H., Wu, Y., Chou, T., & Wu, C.-W. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21186829 · Cited by 18 · see citing works
Dash, B., Chang, Y., & Lukas, R. J. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.264044 · Cited by 17 · see citing works
Wageman, C. R., Marks, M. J., & Grady, S. R. (2013) · Nicotine & Tobacco Research · doi:10.1093/ntr/ntt146 · Cited by 16 · see citing works
Papapostolou, I., Ross‐Kaschitza, D., Bochen, F., Peinelt, C., & Maldifassi, M. C. (2023) · Cells · doi:10.3390/cells12152000 · Cited by 15 · see citing works
Dash, B., Li, M. D., & Lukas, R. J. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.566018 · Cited by 15 · see citing works
McClure‐Begley, T. D., Grady, S. R., Marks, M. J., Collins, A. C., & Stitzel, J. A. (2014) · Biochemical Pharmacology · doi:10.1016/j.bcp.2014.06.010 · Cited by 15 · see citing works
Self-citationNicotinic Acetylcholine Receptors
Lindstrom, J. M. (2010) · Wiley eBooks · doi:10.1002/9780470015902.a0000245.pub2 · Cited by 14 · see citing works
Self-citationWhiteaker, P., & George, A. A. (2023) · Pharmacological Research · doi:10.1016/j.phrs.2023.106743 · Cited by 14 · see citing works
Self-citationMantione, M. E., Micheloni, S., Alcaino, C., New, K., Mazzaferro, S., & Bermúdez, I. (2012) · Future Medicinal Chemistry · doi:10.4155/fmc.12.172 · Cited by 12 · see citing works
Association of CHRNA5 Gene Variants with Crack Cocaine Addiction
Aroche, A. P., Rovaris, D. L., Grevet, E. H., Stolf, A. R., Sanvicente‐Vieira, B., Kessler, F. H. P., DIEMEN, L. V., Grassi‐Oliveira, R., Bau, C. H. D., & Schuch, J. B. (2020) · NeuroMolecular Medicine · doi:10.1007/s12017-020-08596-1 · Cited by 12 · see citing works
More than Smoke and Patches: The Quest for Pharmacotherapies to Treat Tobacco Use Disorder
Moerke, M. J., McMahon, L. R., & Wilkerson, J. L. (2020) · Pharmacological Reviews · doi:10.1124/pr.119.018028 · Cited by 11 · see citing works
Wilking, J. A., & Stitzel, J. A. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2014.11.022 · Cited by 10 · see citing works
Linking the CHRNA5 SNP to drug abuse liability: From circuitry to cellular mechanisms
Brynildsen, J. K., & Blendy, J. A. (2021) · Neuropharmacology · doi:10.1016/j.neuropharm.2021.108480 · Cited by 10 · see citing works
Nagumo, Y., Takeuchi, Y., Imoto, K., & Miyata, M. (2010) · Neuroscience Research · doi:10.1016/j.neures.2010.12.002 · Cited by 9 · see citing works
Climer, S., Templeton, A. R., Garvin, M. R., Jacobson, D., Lane, M. J., Hulver, S., Scheid, B. H., Chen, Z., Cruchaga, C., & Zhang, W. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.01.28.923730 · Cited by 8 · see citing works
Yang, D., Qi, G., Delev, D., Maskos, U., & Feldmeyer, D. (2025) · Translational Psychiatry · doi:10.1038/s41398-025-03230-9 · Cited by 7 · see citing works
“It has been shown that the deletion of the α 5 subunit does not affect the density of α 4 β 2 nAChRs but speci fi cally reduces agonist activation af fi nity [55, 63].”
Asgarihafshejani, A., Nashmi, R., & Delaney, K. R. (2019) · Neuroscience · doi:10.1016/j.neuroscience.2019.07.008 · Cited by 7 · see citing works
Tochon, L., Henkous, N., Besson, M., Maskos, U., & David, V. (2024) · Translational Psychiatry · doi:10.1038/s41398-024-03164-8 · Cited by 6 · see citing works
“In rodents, α 5*nAChRs are expressed in brain regions implicated in reward and aversion, i.e., the dopaminergic mesolimbic and habenulo-interpeduncular pathways, attention processes, impulsivity and memory (including the medial prefrontal cortex and hippocampus) [22, 23].”
Backgroundα4β2 nicotinic acetylcholine receptors intrinsically influence body weight in mice
Dezfuli, G., Olson, T. T., Martin, L. M., Keum, Y., Siegars, B., Desai, A., Uitz, M., Sahibzada, N., Gillis, R. A., & Kellar, K. J. (2019) · Neuropharmacology · doi:10.1016/j.neuropharm.2019.107921 · Cited by 5 · see citing works
α6 nicotinic acetylcholine receptors: A pharmacological challenge with untapped therapeutic promise
Zhang, B., Mao, K., Ma, L., Chen, Y.-S., Ren, M., Xiong, Y., Zhangsun, D., Dong, S., Luo, S., & Gao, B. (2025) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2025.118300 · Cited by 3 · see citing works
Presynaptic Nicotinic Acetylcholine Receptors: Subtypes and Functions
Marks, M. J., Grady, S. R., McClure‐Begley, T. D., O’Neill, H. C., & Zambrano, C. A. (2014) · The Receptors · doi:10.1007/978-1-4939-1167-7_4 · Cited by 1 · see citing works
Yang, D., Qi, G., Delev, D., Maskos, U., & Feldmeyer, D. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.04.12.589167 · Cited by 1 · see citing works
Tochon, L., Pageze, C., Henkous, N., Guillou, J., & David, V. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.01.13.698088 · Cited by 1 · see citing works
Soll, L. G. (2013) · eScholarship@UMassChan · doi:10.13028/m2ng64
“The α−CtxMII insensitive nAChR population is composed of α4β2 and α4α5β2 nAChRs (Champtiaux et al., 2003, Salminen et al., 2004, Brown et al., 2007, Salminen et al., 2007, Grady et al., 2010).”
BackgroundHendrickson, L. M. (2011) · PubMed · doi:10.13028/174w-zb21
“However, studies now indicate that approximately 20 % of all native α4β2 nAChRs also contain the α5 subunit (Brown et al., 2007).”
BackgroundDrenan, R. M., Patzlaff, N. E., & MichaelMcIntosh, J. (2010)
Wilking, J. A., & Stitzel, J. A. (2016) · Neuromethods · doi:10.1007/978-1-4939-3768-4_6
Fox-Loe, A. M. (2016) · UKnowledge (University of Kentucky) · doi:10.13023/etd.2016.461
Targeting Nicotinic Acetylcholine Receptors for the Treatment of Pain
Bağdaş, D., Kyte, S. L., Toma, W. B., Gurun, M. S., & Damaj, M. I. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-813035-3.00033-2
Marks, M. J., Loetz, E. C., Ortiz, N. C., Herder, P., & Collins, A. C. (2020) · Behavioural Pharmacology · doi:10.1097/fbp.0000000000000575
“…in receptors with the α3 and β4 subunits in the autonomic nervous system and almost exclusively with the α4 and β2 subunits in the central nervous system (Brown et al., 2007; Moretti Copyright © 2020 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. et al., 2018).”
BackgroundSelf-citationTochon, L., Pageze, C., Henkous, N., Guillou, J., & David, V. (2026) · iScience · doi:10.1016/j.isci.2026.117950 · Cited by 1 · see citing works
“14”
Intracellular Signaling Contributions to Behaviors Relevant to Nicotine Addiction
Thompson, L. E. (2011) · VCU Scholars Compass (Virginia Commonwealth University) · doi:10.25772/c371-2y50
THE ROLE OF NICOTINIC ACETYLCHOLINE RECEPTORS IN ETHANOL RESPONSIVE BEHAVIORS AND DRINKING
Dawson, A. (2013) · VCU Scholars Compass (Virginia Commonwealth University) · doi:10.25772/e6t8-v015
“…of α-Conotoxin MII- resistant dopamine (DA) release in the mesolimbic dopamine system (MDS) because α5 gene deletion resulted in decreased maximal ACh-stimulated dopamine release and α5* nAChRs were found to be expressed in striatal synaptosomes in the mouse (Grady et al. 2010, Brown et al. 2007).”
Background
- Authors
- Brown, R. W. B., Collins, A. C., Lindstrom, J. M., & Whiteaker, P.
- Affiliations
- University of Colorado Boulder (US)
- University of Pennsylvania (US)
- Corresponding author
- Whiteaker, Paul
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2007-05-21
- Volume
- 103
- Issue
- 1
- Pages
- 204-215
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2062770122
- Cited by
- 88
- References
- 51
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 3 · 2023: 3 · 2021: 2 · 2020: 8 · 2019: 5 · 2018: 1 · 2017: 1 · 2016: 4 · 2015: 6 · 2014: 6 · 2013: 6 · 2012: 4
- FWCI
- 3.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Drug Abuse (R21DA019655, DA-19655, DA 03194, P30DA015663, DA15663, R01DA003194)
- National Institute of Neurological Disorders and Stroke (NS11323, R01NS011323)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Keywords
- nicotinic acetylcholine receptors, alpha5 subunit, agonist affinity, epibatidine binding, thalamus, striatum, nicotine sensitivity, mouse brain
- MeSH terms
- Animals, Behavior, Animal, Binding, Competitive, Brain, Corpus Striatum, Mice, Inbred C57BL, Mice, Neurologic Mutants, Organ Specificity, Pyridines, Receptors, Nicotinic, Rubidium Radioisotopes, Thalamus, Nicotinic Agonists, Bridged Bicyclo Compounds, Heterocyclic, Immunoprecipitation, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
