Nicotinic receptors subunits

Marks, M., Pauly, J., Gross, S. et al. Nicotine binding and nicotinic receptor subunit RNA after chronic nicotine treatment. J. Neurosci. 2765, 1992. 

Nicotinic receptor subunits are part of a large superfamily of ligand-gated channels 202... 

Nicotine is an agonist at the nicotinic acetylcholine receptor (nAChR). Activation of this receptor depolarizes target cells (see Ch. 11). nAChRs are composed of five subunits surrounding a central ion-channel pore. Twelve different nicotinic receptor subunits are expressed in the nervous system (a2-oclO and (32—134). Of these, a subset is expressed in the VTA (a3-a7 and P2—134). It is thought that a7 receptors form homomeric receptors a3, a4 and a6 form heteromeric channels with 02 or 04 and a5 and 03 can associate with other a/0 pairs. Studies in knockout mice implicate several subunits in the ability of nicotine to modulate dopamine neurons (a4, a6, a7, 02, 03) but... 

Wada E, Wada K, Boulter J, Deneris E, Heinemann S, et al. 1989. Distribution of al, a3, a4, and 32 neuronal nicotinic receptor subunit mRNAs in the central nervous system a hybridization histochemical study in the rat. J Comp Neurol 284 314-335. 

Marks Ml, Campbell SM, Romm E, Collins AC (1991) Genotype influences the development of tolerance to nicotine in the mouse. J Pharmacol Exp Ther 259 392 02 Marks MJ, Pauly JR, Gross SD, Deneris ES, Hermans-Borgmeyer I, Heinemann SF, Collins AC (1992) Nicotine binding and nicotinic receptor subunit RNA after chronic nicotine treatment. J Neurosci 12 2765-2784... 

Marks MJ, Whiteaker P, Collins AC (2006) Deletion of the a7, [12 and 34 nicotinic receptor subunit genes identifies highly expressed subtypes with relatively low affinity for [ H]-epibatidine. Mol Pharmacol 70 947-959... 

Sgard F, Charpantier E, Bertrand S, Walker N, Caput D, Graham D, Bertrand D, Besnard F (2002) A novel human nicotinic receptor subunit, alO, that confers functionality to the a9-subunit. Mol Pharmacol 61 150-159... 

Kerchove d Exaerde, A., Huchet, M., Damaj, M. I. Reduced antinociception in mice lacking neuronal nicotinic receptor subunits. Nature 1999, 398, 805-810. 

DeLuca V, Wong AH. Muller DJ, Wong GW, Tyndale RF, et al. 2004a. Evidence for association between smoking and alpha7 nicotinic receptor subunit gene in schizophrenic patients. Neuropsychopharmacology 29 1522-1526. 

Raux G, Bonnet-Brilhault F, Louchart S, et al. 2002. The -2bp deletion in exon 6 of the alpha 7-like nicotinic receptor subunit gene is a risk factor for the P50 sensory gating deficit. Mol Psychiatry 7 1006-1011. 

De Luca V, Likhodi O, Van Tol HH, Kennedy JL, Wong AH. 2006. Regulation of alpha7-nicotinic receptor subunit and alpha7-like gene expression in the prefrontal cortex of patients with bipolar disorder and schizophrenia. Acta Psy-chiatr Scand 114 211-215. 

Quik M, Polonskaya Y, Gillespie A, Jakowec M, Lloyd GK, et al. 2000. Localization of nicotinic receptor subunit mRNAs in monkey brain by in situ hybridization. J Comp Neurol 425 58-69. 

Berrettini W, Yuan X, Tozzi F, Song K, Francks C, CMcoat H, Waterworth D, Muglia P, Mooser V (2008) Alpha-5/alpha-3 nicotinic receptor subunit alleles increase risk for heavy smoking. Mol Psychiatry 13 368-373... 

Guan ZZ, Zhang X, Ravid R, Nordberg A (2000) Decreased protein levels of nicotinic receptor subunits in the hippocampus and tempered cortex of patients with Alzheimer s disease. J... 

Hellstrom-Lindahl E, Mousavi M, Ravid R, Nordbeig A (2(X)4) Reduced levels of Abeta 40 and Abeta 42 in brains of smoking controls and Alzheimer s patients. Neurobiol Dis 15 351-360 Hellstrom-Lindahl E, Mousavi M, Zhang X, Ravid R, Nordbeig A (1999) Regional distribution of nicotinic receptor subunit mRNAs in human biain comparison between Alzheimer and normal... 

Terzano S, Court JA, Fomasari D, Griffiths M, Spurden DP, Uoyd S, Perry RH, Perry EK, Qementi F (1998) Expression of the alpha3 nicotinic receptor subunit mRNA in aging and Alzheimer s disease. Brain Res Mol Brain Res 63 72-78... 

The cholinergic system in autism has been investigated in a number of post-mortem studies (Table 1). In the parietal and frontal cortices of autistic adult subjects, levels of nicotinic receptors were 65-73% lower than in controls (Perry et al., 2001). In the parietal cortex specifically, there were lower levels of a4 and f)2 nicotinic receptor subunits, the high-affinity-type nicotinic receptor (Fig. 4). These abnormalities... 

In the thalamus, nicotinic receptor subunits were decreased in the numbers of a and P2 immunoreactive neurons in the paraventricular nucleus (PV) and nucleus reuniens (NR) in autistic subjects (Ray et al., 2005 Fig. 4). These deficits in nicotinic receptor subunits perhaps result in the failure of the PV and NR (and so the thalamus) to correctly modulate sensory input. This effect would then be transferred throughout the limbic system to other parts of the brain, contributing to the incorrect sensory processing found in autism (Martin-Ruiz et al., 2004). The co-expression of a and glutamic acid decarboxylase (GAD) study indicated that despite the decrease in a7, the expression of GAD in the PV was similar in both autistic and control subjects (Ray et al., 2005). This suggests that the decrease in a7 subunits in the thalamus is not associated with the GABAergic system. 

The al subunit is different from the other neuronal nicotine receptor subunits in forming functional channels in the homomeric configuration (Seguela et al., 1993) that, unlike other nicotine receptors of the brain, are sensitive to a-bungarotoxin (aBTX). 

Autosomal dominant nocturnal frontal-lobe epilepsy (ADNFLE) is a form of partial epilepsy which is characterized by frontal-lobe motor seizures occurring during sleep (Philips et al., 1998). This disorder has been linked to a mutation in the channel-lining domain (M2) of the a 4 nicotinic receptor subunit with use-dependent potentiation of the electrophysiological response to nicotinic agonists (Lena and Changeux, 1998). If the symptoms of ADNFLE are secondary to overactivity of this receptor or unusual potentiation, then nicotinic antagonists such as mecamylamine may be helpful. 

Marubio, L.M., del Mar Arroyo-Jimenez, M., Cordero-Erausquin, M., Lena, C., Le Novere, N., de Kerchove d Exaerde, A., Huchet, M., Damaj, M.I., Changeux, J.-P., 1999. Reduced antinociception in mice lacking neuronal nicotinic receptor subunits. Nature (London) 398, 305-810. 

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