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A Review of the Cholinergic System and Therapeutic Approaches to Treat Brain Disorders

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Behavioral Pharmacology of the Cholinergic System

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 45))

Abstract

Since its identification over a hundred years ago, the neurotransmitter acetylcholine (ACh) has proven to play an essential role in supporting many diverse functions. Some well-characterized functions include: chemical transmission at the neuromuscular junction; autonomic function in the peripheral nervous system; and, sustained attention, sleep/wake regulation, and learning and memory within the central nervous system. Within the brain, major cholinergic projection pathways from the basal forebrain and the brainstem support these centrally mediated processes, and dysregulation of the cholinergic system is implicated in cognitive decline associated with aging and dementias including Alzheimer’s disease. ACh exerts its effects by binding to two different membrane-bound receptor classes: (1) G‑protein coupled muscarinic acetylcholine receptors (mAChRs), and (2) ligand-gated nicotinic acetylcholine receptors (nAChRs). These receptor systems are described in detail within this chapter along with discussion on the successes and failures of synthetic ligands designed to selectively target receptor subtypes for treating brain disorders. New molecular approaches and advances in our understanding of the target biology combined with opportunities to re-purpose existing cholinergic drugs for new indications continue to highlight the exciting opportunities for modulating this system for therapeutic purposes.

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References

  • Ahmed T, Zahid S, Mahboob A, Farhat SM (2017) Cholinergic system and post-translational modifications: an insight on the role in Alzheimer’s disease. Curr Neuropharmacol 15(4):480–494

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Alkondon M, Braga MF, Pereira EF, Maelicke A, Albuquerque EX (2000) alpha7 nicotinic acetylcholine receptors and modulation of gabaergic synaptic transmission in the hippocampus. Eur J Pharmacol 393(1–3):59–67

    Article  CAS  PubMed  Google Scholar 

  • Araud T, Graw S, Berger R, Lee M, Neveu E, Bertrand D, Leonard S (2011) The chimeric gene CHRFAM7A, a partial duplication of the CHRNA7 gene, is a dominant negative regulator of alpha7∗nAChR function. Biochem Pharmacol 82(8):904–914

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Baird A, Coimbra R, Dang X, Eliceiri BP, Costantini TW (2016) Up-regulation of the human-specific CHRFAM7A gene in inflammatory bowel disease. BBA Clin 5:66–71

    Article  PubMed  PubMed Central  Google Scholar 

  • Ballivet M, Nef P, Couturier S, Rungger D, Bader CR, Bertrand D, Cooper E (1988) Electrophysiology of a chick neuronal nicotinic acetylcholine receptor expressed in Xenopus oocytes after cDNA injection. Neuron 1(9):847–852

    Article  CAS  PubMed  Google Scholar 

  • Barbier AJ, Hilhorst M, Van Vliet A, Snyder P, Palfreyman MG, Gawryl M, Dgetluck N, Massaro M, Tiessen R, Timmerman W, Hilt DC (2015) Pharmacodynamics, pharmacokinetics, safety, and tolerability of encenicline, a selective α7 nicotinic receptor partial agonist, in single ascending-dose and bioavailability studies. Clin Ther 37(2):311–324

    Article  CAS  PubMed  Google Scholar 

  • Beckmann J, Lips KS (2013) The non-neuronal cholinergic system in health and disease. Pharmacology 92(5–6):286–302

    Article  CAS  PubMed  Google Scholar 

  • Bencherif M, Lippiello PM (2009) Alpha7 neuronal nicotinic receptors: the missing link to understanding Alzheimer's etiopathology? Med Hypotheses 74(2):281–285

    Article  PubMed  CAS  Google Scholar 

  • Bender AM, Garrison AT, Lindsley CW (2019) The muscarinic acetylcholine receptor M5: therapeutic implications and allosteric modulation. ACS Chem Neurosci 10(3):1025–1034

    Article  CAS  PubMed  Google Scholar 

  • Berger T, Lüscher H-R (2003) Timing and precision of spike initiation in layer V pyramidal cells of the rat somatosensory cortex. Cereb Cortex 13(3):274–281

    Article  PubMed  Google Scholar 

  • Bertrand D, Cooper E, Valera S, Rungger D, Ballivet M (1991) Electrophysiology of neuronal nicotinic acetylcholine receptors expressed in Xenopus oocytes following nuclear injection of genes or cDNA. In: Conn M (ed) Methods in neuroscience, vol 4. Academic Press, New York, pp 174–193

    Google Scholar 

  • Bertrand D, Galzi JL, Devillers-Thiery A, Bertrand S, Changeux JP (1993a) Mutations at two distinct sites within the channel domain M2 alter calcium permeability of neuronal alpha 7 nicotinic receptor. Proc Natl Acad Sci U S A 90(15):6971–6975

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bertrand D, Galzi JL, Devillers-Thiery A, Bertrand S, Changeux JP (1993b) Stratification of the channel domain in neurotransmitter receptors. Curr Opin Cell Biol 5(4):688–693

    Article  CAS  PubMed  Google Scholar 

  • Bertrand D, Lee CH, Flood D, Marger F, Donnelly-Roberts D (2015) Therapeutic potential of alpha7 nicotinic acetylcholine receptors. Pharmacol Rev 67(4):1025–1073

    Article  CAS  PubMed  Google Scholar 

  • Besson M, Granon S, Mameli-Engvall M, Cloëz-Tayarani I, Maubourguet N, Cormier A, Cazala P, David V, Changeux J-P, Faure P (2007) Long-term effects of chronic nicotine exposure on brain nicotinic receptors. Proc Natl Acad Sci U S A 104(19):8155–8160

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Besson M, Guiducci S, Granon S, Guilloux J-P, Guiard B, Repérant C, Faure P, Pons S, Cannazza G, Zoli M, Gardier AM, Maskos U (2016) Alterations in alpha5∗ nicotinic acetylcholine receptors result in midbrain- and hippocampus-dependent behavioural and neural impairments. Psychopharmacology (Berl) 233(18):3297–3314

    Article  CAS  Google Scholar 

  • Billard W, Binch H 3rd, Crosby G, McQuade RD (1995) Identification of the primary muscarinic autoreceptor subtype in rat striatum as m2 through a correlation of in vivo microdialysis and in vitro receptor binding data. J Pharmacol Exp Ther 273(1):273–279

    CAS  PubMed  Google Scholar 

  • Bock A, Schrage R, Mohr K (2018) Allosteric modulators targeting CNS muscarinic receptors. Neuropharmacology 136(Pt C):427–437

    Article  CAS  PubMed  Google Scholar 

  • Bonfante-Cabarcas R, Swanson KL, Alkondon M, Albuquerque EX (1996) Diversity of nicotinic acetylcholine receptors in rat hippocampal neurons. IV. Regulation by external Ca++ of alpha-bungarotoxin-sensitive receptor function and of rectification induced by internal Mg++. J Pharmacol Exp Ther 277(1):432–444

    CAS  PubMed  Google Scholar 

  • Brown RWB, Collins AC, Lindstrom JM, Whiteaker P (2007) Nicotinic alpha5 subunit deletion locally reduces high-affinity agonist activation without altering nicotinic receptor numbers. J Neurochem 103(1):204–215

    CAS  PubMed  Google Scholar 

  • Buisson B, Gopalakrishnan M, Arneric SP, Sullivan JP, Bertrand D (1996) Human alpha4beta2 neuronal nicotinic acetylcholine receptor in HEK 293 cells: a patch-clamp study. J Neurosci 16(24):7880–7891

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bymaster FP, Carter PA, Yamada M, Gomeza J, Wess J, Hamilton SE, Nathanson NM, McKinzie DL, Felder CC (2003) Role of specific muscarinic receptor subtypes in cholinergic parasympathomimetic responses, in vivo phosphoinositide hydrolysis, and pilocarpine-induced seizure activity. Eur J Neurosci 17(7):1403–1410

    Article  PubMed  Google Scholar 

  • Callahan PM, Bertrand D, Bertrand S, Plagenhoef MR, Terry AV Jr (2017) Tropisetron sensitizes alpha7 containing nicotinic receptors to low levels of acetylcholine in vitro and improves memory-related task performance in young and aged animals. Neuropharmacology 117:422–433

    Article  CAS  PubMed  Google Scholar 

  • Castro NG, Albuquerque EX (1995) Alpha-Bungarotoxin-sensitive hippocampal nicotinic receptor channel has a high calcium permeability. Biophys J 68(2):516–524

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cheng Q, Yakel JL (2014) Presynaptic α7 nicotinic acetylcholine receptors enhance hippocampal mossy Fiber glutamatergic transmission via PKA activation. J Neurosci 34(1):124–133

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Corringer PJ, Bertrand S, Galzi JL, Devillers-Thiery A, Changeux JP, Bertrand D (1999) Mutational analysis of the charge selectivity filter of the alpha 7 nicotinic acetylcholine receptor. Neuron 22(4):831–843

    Article  CAS  PubMed  Google Scholar 

  • Costantini TW, Dang X, Yurchyshyna MV, Coimbra R, Eliceiri BP, Baird A (2015) A human-specific α7-nicotinic acetylcholine receptor gene in human leukocytes: identification, regulation and the consequences of CHRFAM7A expression. Mol Med 3(21):323–336

    Article  CAS  Google Scholar 

  • Criscuolo C, Accorroni A, Domenici L, Origlia N (2015) Impaired synaptic plasticity in the visual cortex of mice lacking alpha7-nicotinic receptor subunit. Neuroscience 294:166–171

    Article  CAS  PubMed  Google Scholar 

  • Crook JM, Tomaskovic-Crook E, Copolov DL, Dean B (2001) Low muscarinic receptor binding in prefrontal cortex from subjects with schizophrenia: a study of Brodmann's areas 8, 9, 10, and 46 and the effects of neuroleptic drug treatment. Am J Psychiatry 158(6):918–925

    Article  CAS  PubMed  Google Scholar 

  • Curtis L, Buisson B, Bertrand S, Bertrand D (2002) Potentiation of human alpha4beta2 neuronal nicotinic acetylcholine receptor by estradiol. Mol Pharmacol 61(1):127–135

    Article  CAS  PubMed  Google Scholar 

  • Dang X, Eliceiri BP, Baird A, Costantini TW (2015) CHRFAM7A: a human-specific α7-nicotinic acetylcholine receptor gene shows differential responsiveness of human intestinal epithelial cells to LPS. FASEB J 29(6):2292–2302

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dani JA, Bertrand D (2007) Nicotinic acetylcholine receptors and nicotinic cholinergic mechanisms of the central nervous system. Annu Rev Pharmacol Toxicol 47:699–729

    Article  CAS  PubMed  Google Scholar 

  • Dani JA, Radcliffe KA, Pidoplichko VI (2000) Variations in desensitization of nicotinic acetylcholine receptors from hippocampus and midbrain dopamine areas. Eur J Pharmacol 393(1–3):31–38

    Article  CAS  PubMed  Google Scholar 

  • Dasari S, Hill C, Gulledge AT (2017) A unifying hypothesis for M1 muscarinic receptor signalling in pyramidal neurons. J Physiol 595(5):1711–1723

    Article  CAS  PubMed  Google Scholar 

  • de Jonge WJ, Ulloa L (2007) The alpha7 nicotinic acetylcholine receptor as a pharmacological target for inflammation. Br J Pharmacol 151(7):915–929

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • de Lucas-Cerrillo AM, Maldifassi MC, Arnalich F, Renart J, Atienza G, Serantes R, Cruces J, Sánchez-Pacheco A, Andrés-Mateos E, Montiel C (2011) Function of partially duplicated human α77 nicotinic receptor subunit CHRFAM7A gene: potential implications for the cholinergic anti-inflammatory response. J Biol Chem 286(1):594–606

    Article  PubMed  CAS  Google Scholar 

  • Dennis SH, Pasqui F, Colvin EM, Sanger H, Mogg AJ, Felder CC, Broad LM, Fitzjohn SM, Isaac JT, Mellor JR (2016) Activation of muscarinic M1 acetylcholine receptors induces long-term potentiation in the Hippocampus. Cereb Cortex 26(1):414–426

    Article  PubMed  Google Scholar 

  • Devillers-Thiery A, Galzi JL, Bertrand S, Changeux JP, Bertrand D (1992) Stratified organization of the nicotinic acetylcholine receptor channel. Neuroreport 3(11):1001–1004

    Article  CAS  PubMed  Google Scholar 

  • Dhawan S, Cailotto C, Harthoorn LF, de Jonge WJ (2012) Cholinergic signalling in gut immunity. Life Sci 91(21–22):1038–1042

    Article  CAS  PubMed  Google Scholar 

  • Elgoyhen AB, Johnson DS, Boulter J, Vetter DE, Heinemann S (1994) Alpha 9: an acetylcholine receptor with novel pharmacological properties expressed in rat cochlear hair cells. Cell 79(4):705–715

    Article  CAS  PubMed  Google Scholar 

  • Felder CC, Goldsmith PJ, Jackson K, Sanger HE, Evans DA, Mogg AJ, Broad LM (2018) Current status of muscarinic M1 and M4 receptors as drug targets for neurodegenerative diseases. Neuropharmacology 136(Pt C):449–458

    Article  CAS  PubMed  Google Scholar 

  • Fenster CP, Rains MF, Noerager B, Quick MW, Lester RA (1997) Influence of subunit composition on desensitization of neuronal acetylcholine receptors at low concentrations of nicotine. J Neurosci 17(15):5747–5759

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Flomen RH, Shaikh M, Walshe M, Schulze K, Hall M-H, Picchioni M, Rijsdijk F, Toulopoulou T, Kravariti E, Murray RM, Asherson P, Makoff AJ, Bramon E (2012) Association between the 2-bp deletion polymorphism in the duplicated version of the alpha7 nicotinic receptor gene and P 50 sensory gating. Eur J Hum Genet 21(1):76–81

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Forster I, Bertrand D (1995) Inward rectification of neuronal nicotinic acetylcholine receptors investigated by using the homomeric alpha 7 receptor. Proc Biol Sci 260(1358):139–148

    Article  CAS  PubMed  Google Scholar 

  • Fucile S, Renzi M, Lauro C, Limatola C, Ciotti T, Eusebi F (2004) Nicotinic cholinergic stimulation promotes survival and reduces motility of cultured rat cerebellar granule cells. Neuroscience 127(1):53–61

    Article  CAS  PubMed  Google Scholar 

  • Fucile S, Sucapane A, Eusebi F (2005) Ca2+ permeability of nicotinic acetylcholine receptors from rat dorsal root ganglion neurones. J Physiol 565(Pt 1):219–228

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Galzi JL, Devillers-Thiery A, Hussy N, Bertrand S, Changeux JP, Bertrand D (1992) Mutations in the channel domain of a neuronal nicotinic receptor convert ion selectivity from cationic to anionic. Nature 359(6395):500–505

    Article  CAS  PubMed  Google Scholar 

  • Gault J, Robinson M, Berger R, Drebing C, Logel J, Hopkins J, Moore T, Jacobs S, Meriwether J, Choi MJ, Kim EJ, Walton K, Buiting K, Davis A, Breese C, Freedman R, Leonard S (1998) Genomic organization and partial duplication of the human alpha7 neuronal nicotinic acetylcholine receptor gene (CHRNA7). Genomics 52(2):173–185

    Article  CAS  PubMed  Google Scholar 

  • Gautam D, Han SJ, Hamdan FF, Jeon J, Li B, Li JH, Cui Y, Mears D, Lu H, Deng C, Heard T, Wess J (2006) A critical role for beta cell M3 muscarinic acetylcholine receptors in regulating insulin release and blood glucose homeostasis in vivo. Cell Metab 3(6):449–461

    Article  CAS  PubMed  Google Scholar 

  • Gerzanich V, Kuryatov A, Anand R, Lindstrom J (1997) "Orphan" alpha 6 nicotinic AChR subunit can form a functional heteromeric acetylcholine receptor. Mol Pharmacol 51(2):320–327

    Article  CAS  PubMed  Google Scholar 

  • Gerzanich V, Wang F, Kuryatov A, Lindstrom J (1998) Alpha 5 subunit alters desensitization, pharmacology, Ca++ permeability and Ca++ modulation of human neuronal alpha 3 nicotinic receptors. J Pharmacol Exp Ther 286(1):311–320

    CAS  PubMed  Google Scholar 

  • Glaser T, Arnaud Sampaio VF, Lameu C, Ulrich H (2018) Calcium signalling: a common target in neurological disorders and neurogenesis. Semin Cell Dev Biol S1084-9521(18):30068–30065

    Google Scholar 

  • Godyń J, Jończyk J, Panek D, Malawska B (2016) Therapeutic strategies for Alzheimer’s disease in clinical trials. Pharmacol Rep 68(1):127–138

    Article  PubMed  CAS  Google Scholar 

  • Gotti C, Moretti M, Gaimarri A, Zanardi A, Clementi F, Zoli M (2007) Heterogeneity and complexity of native brain nicotinic receptors. Biochem Pharmacol 74(8):1102–1111

    Article  CAS  PubMed  Google Scholar 

  • Grady SR, Salminen O, McIntosh JM, Marks MJ, Collins AC (2010) Mouse striatal dopamine nerve terminals express alpha4alpha5beta2 and two stoichiometric forms of alpha4beta2∗-nicotinic acetylcholine receptors. J Mol Neurosci 40(1–2):91–95

    Article  CAS  PubMed  Google Scholar 

  • Gubbins EJ, Gopalakrishnan M, Li J (2010) Alpha7 nAChR-mediated activation of MAP kinase pathways in PC12 cells. Brain Res 1328:1–11

    Article  CAS  PubMed  Google Scholar 

  • Haga K, Kruse AC, Asada H, Yurugi-Kobayashi T, Shiroishi M, Zhang C, Weis WI, Okada T, Kobilka BK, Haga T, Kobayashi T (2012) Structure of the human M2 muscarinic acetylcholine receptor bound to an antagonist. Nature 482(7386):547–551

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Haghighi AP, Cooper E (2000) A molecular link between inward rectification and calcium permeability of neuronal nicotinic acetylcholine alpha3beta4 and alpha4beta2 receptors. J Neurosci 20(2):529–541

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hampel H, Mesulam MM, Cuello AC, Khachaturian AS, Vergallo A, Farlow MR, Snyder PJ, Giacobini E, Khachaturian ZS (2019) Revisiting the cholinergic hypothesis in Alzheimer’s disease: emerging evidence from translational and clinical research. J Prev Alzheimers Dis 6(1):2–15

    CAS  PubMed  Google Scholar 

  • Hayward A, Adamson L, Neill JC (2017) Partial agonism at the α7 nicotinic acetylcholine receptor improves attention, impulsive action and vigilance in low attentive rats. Eur Neuropsychopharmacol 7(4):325–335

    Article  CAS  Google Scholar 

  • Hilf RJC, Dutzler R (2009) Structure of a potentially open state of a proton-activated pentameric ligand-gated ion channel. Nature 457(7225):115–118

    Article  CAS  PubMed  Google Scholar 

  • Hoda JC, Gu W, Friedli M, Phillips HA, Bertrand S, Antonarakis SE, Goudie D, Roberts R, Scheffer IE, Marini C, Patel J, Berkovic SF, Mulley JC, Steinlein OK, Bertrand D (2008) Human nocturnal frontal lobe epilepsy: pharmocogenomic profiles of pathogenic nicotinic acetylcholine receptor beta-subunit mutations outside the ion channel pore. Mol Pharmacol 74(2):379–391

    Article  CAS  PubMed  Google Scholar 

  • Hogg RC, Bertrand D (2007) Partial agonists as therapeutic agents at neuronal nicotinic acetylcholine receptors. Biochem Pharmacol 73(4):459–468

    Article  CAS  PubMed  Google Scholar 

  • Hou Z, Zhou Y, Yang H, Liu Y, Mao X, Qin X, Li X, Zhang X, Hu Y (2018) Alpha7 nicotinic acetylcholine receptor activation protects against myocardial reperfusion injury through modulation of autophagy. Biochem Biophys Res Commun 500(2):357–364

    Article  CAS  PubMed  Google Scholar 

  • Ihnatovych I, Nayak TK, Ouf A, Sule N, Birkaya B, Chaves L, Auerbach A, Szigeti K (2019) iPSC model of CHRFAM7A effect on α7 nicotinic acetylcholine receptor function in the human context. Transl Psychiatry 9(1):59

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Improgo MRD, Scofield MD, Tapper AR, Gardner PD (2010) The nicotinic acetylcholine receptor CHRNA5/A3/B4 gene cluster: dual role in nicotine addiction and lung cancer. Prog Neurobiol 92:212–226

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Janssen I, Shepard DS, Katzmarzyk PT, Roubenoff R (2004) The healthcare costs of sarcopenia in the United States. J Am Geriatr Soc 52(1):80–85

    Article  PubMed  Google Scholar 

  • Jones IW, Wonnacott S (2004) Precise localization of alpha7 nicotinic acetylcholine receptors on glutamatergic axon terminals in the rat ventral tegmental area. J Neurosci 24(50):11244–11252

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Juneja P, Horlacher R, Bertrand D, Krause R, Marger F, Welte W (2014) An internally modulated, thermostable, pH-sensitive Cys loop receptor from the hydrothermal vent worm Alvinella pompejana. J Biol Chem 289(21):15130–15140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kabbani N, Nichols RA (2018) Beyond the channel: metabotropic signaling by nicotinic receptors. Trends Pharmacol Sci 39(4):354–366

    Article  CAS  PubMed  Google Scholar 

  • Katz E, Verbitsky M, Rothlin CV, Vetter DE, Heinemann SF, Elgoyhen AB (2000) High calcium permeability and calcium block of the alpha 9 nicotinic acetylcholine receptor. Hear Res 141(1–2):117–128

    Article  CAS  PubMed  Google Scholar 

  • Keefe RSE, Meltzer HA, Dgetluck N, Gawryl M, Koenig G, Moebius HJ, Lombardo I, Hilt DC (2015) Randomized, double-blind, placebo-controlled study of Encenicline, an Alpha-7 nicotinic acetylcholine receptor agonist as a treatment for cognitive impairment in schizophrenia. Neuropsychopharmacology 40(13):3053–3060

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Keramidas A, Moorhouse AJ, French CR, Schofield PR, Barry PH (2000) M2 pore mutations convert the glycine receptor channel from being anion- to cation-selective. Biophys J 79(1):247–259

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • King JR, Kabbani N (2018) Alpha 7 nicotinic receptors attenuate neurite development through calcium activation of calpain at the growth cone. PLoS One 13(5):e0197247

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • King JR, Nordman JC, Bridges SP, Lin M-K, Kabbani N (2015) Identification and characterization of a G protein-binding cluster in α7 nicotinic acetylcholine receptors. J Biol Chem 290(33):20060–20070

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Klink R, de Kerchove d’Exaerde A, Zoli M, Changeux JP (2001) Molecular and physiological diversity of nicotinic acetylcholine receptors in the midbrain dopaminergic nuclei. J Neurosci 21(5):1452–1463

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Krejci A, Michal P, Jakubik J, Ricny J, Dolezal V (2004) Regulation of signal transduction at M2 muscarinic receptor. Physiol Res 53(Suppl 1):S131–S140

    CAS  PubMed  Google Scholar 

  • Kruse AC, Hu J, Pan AC, Arlow DH, Rosenbaum DM, Rosemond E, Green HF, Liu T, Chae PS, Dror RO, Shaw DE, Weis WI, Wess J, Kobilka BK (2012) Structure and dynamics of the M3 muscarinic acetylcholine receptor. Nature 482(7386):552–556

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kruse AC, Hu J, Kobilka BK, Wess J (2014) Muscarinic acetylcholine receptor X-ray structures: potential implications for drug development. Curr Opin Pharmacol 16:24–30

    Article  CAS  PubMed  Google Scholar 

  • Kuner R, Köhr G, Grünewald S, Eisenhardt G, Bach A, Kornau H-C (1999) Role of Heteromer formation in GABAB receptor function. Science 283:74–77

    Article  CAS  PubMed  Google Scholar 

  • Kunii Y, Zhang W, Xu Q, Hyde TM, McFadden W, Shin JH, Deep-Soboslay A, Ye T, Li C, Kleinman JE, Wang KH, Lipska BK (2015) CHRNA7 and CHRFAM7A mRNAs: co-localized and their expression levels altered in the postmortem dorsolateral prefrontal cortex in major psychiatric disorders. Am J Psychiatry 172(11):1122–1130

    Article  PubMed  Google Scholar 

  • Kuryatov A, Onksen J, Lindstrom J (2008) Roles of accessory subunits in alpha4beta2(∗) nicotinic receptors. Mol Pharmacol 74(1):132–143

    Article  CAS  PubMed  Google Scholar 

  • Lamotte d’Incamps B, Zorbaz T, Dingova D, Krejci E, Ascher P (2018) Stoichiometry of the Heteromeric nicotinic receptors of the Renshaw cell. J Neurosci 38(21):4943–4956

    Article  PubMed  PubMed Central  Google Scholar 

  • Langmead CJ, Watson J, Reavill C (2008) Muscarinic acetylcholine receptors as CNS drug targets. Pharmacol Ther 117(2):232–243

    Article  CAS  PubMed  Google Scholar 

  • Lasala M, Fabiani C, Corradi J, Antollini S, Bouzat C (2019) Molecular modulation of human alpha7 nicotinic receptor by amyloid-beta peptides. Front Cell Neurosci 13:37

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lester RA, Dani JA (1995) Acetylcholine receptor desensitization induced by nicotine in rat medial habenula neurons. J Neurophysiol 74(1):195–206

    Article  CAS  PubMed  Google Scholar 

  • Levey AI (1996) Muscarinic acetylcholine receptor expression in memory circuits: implications for treatment of Alzheimer disease. Proc Natl Acad Sci U S A 93(24):13541–13546

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Levey AI, Kitt CA, Simonds WF, Price DL, Brann MR (1991) Identification and localization of muscarinic acetylcholine receptor proteins in brain with subtype-specific antibodies. J Neuroscience 11:3218–3226

    Article  CAS  Google Scholar 

  • Levey AI, Edmunds SM, Heilman CJ, Desmond TJ, Frey KA (1994) Localization of muscarinic m3 receptor protein and M3 receptor binding in rat brain. Neuroscience 63(1):207–221

    Article  CAS  PubMed  Google Scholar 

  • Ma K-G, Qian Y-H (2019) Alpha 7 nicotinic acetylcholine receptor and its effects on Alzheimer's disease. Neuropeptides 73:96–106

    Article  CAS  PubMed  Google Scholar 

  • Maanen MAV, Stoof SP, Zanden EPVD, Jonge WJD, Janssen RA, Fischer DF, Vandeghinste N, Brys R, Vervoordeldonk MJ, Tak PP (2009) The alpha7 nicotinic acetylcholine receptor on fibroblast-like synoviocytes and in synovial tissue from rheumatoid arthritis patients: a possible role for a key neurotransmitter in synovial inflammation. Arthritis Rheum 60(5):1272–1281

    Article  PubMed  Google Scholar 

  • Maeda S, Qu Q, Robertson MJ, Skiniotis G, Kobilka BK (2019) Structures of the M1 and M2 muscarinic acetylcholine receptor/G-protein complexes. Science 364(6440):552–557

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marrero MB, Bencherif M (2009) Convergence of alpha 7 nicotinic acetylcholine receptor-activated pathways for anti-apoptosis and anti-inflammation: central role for JAK2 activation of STAT3 and NF-kappa B. Brain Res 1256:1–7

    Article  CAS  PubMed  Google Scholar 

  • Marsango S, Ward R, Alvarez-Curto E, Milligan G (2018) Muscarinic receptor oligomerization. Neuropharmacology 136:401–410

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matsui M, Motomura D, Karasawa H, Fujikawa T, Jiang J, Komiya Y, Takahashi S, Taketo MM (2000) Multiple functional defects in peripheral autonomic organs in mice lacking muscarinic acetylcholine receptor gene for the M3 subtype. Proc Natl Acad Sci U S A 97(17):9579–9584

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McGehee DS, Heath MJ, Gelber S, Devay P, Role LW (1995) Nicotine enhancement of fast excitatory synaptic transmission in CNS by presynaptic receptors. Science 269(5231):1692–1696

    Article  CAS  PubMed  Google Scholar 

  • Morales-Perez CL, Noviello CM, Hibbs RE (2016) X-ray structure of the human α4β2 nicotinic receptor. Nature 538(7625):411–415

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nelson ME, Wang F, Kuryatov A, Choi CH, Gerzanich V, Lindstrom J (2001) Functional properties of human nicotinic AChRs expressed by IMR-32 neuroblastoma cells resemble those of alpha3beta4 AChRs expressed in permanently transfected HEK cells. J Gen Physiol 118(5):563–582

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nelson ME, Kuryatov A, Choi CH, Zhou Y, Lindstrom J (2003) Alternate stoichiometries of alpha4beta2 nicotinic acetylcholine receptors. Mol Pharmacol 63(2):332–341

    Article  CAS  PubMed  Google Scholar 

  • Nemecz Á, Prevost MS, Menny A, Corringer P-J (2016) Emerging molecular mechanisms of signal transduction in Pentameric ligand-gated ion channels. Neuron 90(3):452–470

    Article  CAS  PubMed  Google Scholar 

  • Nie L, Song H, Chen M-F, Chiamvimonvat N, Beisel KW, Yamoah EN, Vázquez AE (2004) Cloning and expression of a small-conductance Ca (2+)-activated K+ channel from the mouse cochlea: coexpression with alpha9/alpha10 acetylcholine receptors. J Neurophysiol 91(4):1536–1544

    Article  CAS  PubMed  Google Scholar 

  • Ochoa EL, Chattopadhyay A, McNamee MG (1989) Desensitization of the nicotinic acetylcholine receptor: molecular mechanisms and effect of modulators. Cell Mol Neurobiol 9(2):141–178

    Article  CAS  PubMed  Google Scholar 

  • Paradiso K, Brehm P (1998) Long-term desensitization of nicotinic acetylcholine receptors is regulated via protein kinase A-mediated phosphorylation. J Neurosci 18(22):9227–9237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Paradiso K, Zhang J, Steinbach JH (2001) The C terminus of the human nicotinic alpha4beta2 receptor forms a binding site required for potentiation by an estrogenic steroid. J Neurosci 21(17):6561–6568

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Peng H, Ferris RL, Matthews T, Hiel H, Lopez-Albaitero A, Lustig LR (2004) Characterization of the human nicotinic acetylcholine receptor subunit alpha (alpha) 9 (CHRNA9) and alpha (alpha) 10 (CHRNA10) in lymphocytes. Life Sci 76(3):263–280

    Article  CAS  PubMed  Google Scholar 

  • Perez-Lloret S, Barrantes FJ (2016) Deficits in cholinergic neurotransmission and their clinical correlates in Parkinson’s disease. NPJ Parkinsons Dis 2:16001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Perry DC, Xiao Y, Nguyen HN, Musachio JL, Dávila-García MI, Kellar KJ (2002) Measuring nicotinic receptors with characteristics of alpha4beta2, alpha3beta2 and alpha3beta4 subtypes in rat tissues by autoradiography. J Neurochem 82(3):468–481

    Article  CAS  PubMed  Google Scholar 

  • Prickaerts J, van Goethem NP, Chesworth R, Shapiro G, Boess FG, Methfessel C, Reneerkens OA, Flood DG, Hilt D, Gawryl M, Bertrand S, Bertrand D, Konig G (2012) EVP-6124, a novel and selective alpha7 nicotinic acetylcholine receptor partial agonist, improves memory performance by potentiating the acetylcholine response of alpha7 nicotinic acetylcholine receptors. Neuropharmacology 62(2):1099–1110

    Article  CAS  PubMed  Google Scholar 

  • Rathouz MM, Vijayaraghavan S, Berg DK (1995) Acetylcholine differentially affects intracellular calcium via nicotinic and muscarinic receptors on the same population of neurons. J Biol Chem 270(24):14366–14375

    Article  CAS  PubMed  Google Scholar 

  • Razani-Boroujerdi S, Boyd RT, Dávila-García MI, Nandi JS, Mishra NC, Singh SP, Pena-Philippides JC, Langley R, Sopori ML (2007) T cells express alpha7-nicotinic acetylcholine receptor subunits that require a functional TCR and leukocyte-specific protein tyrosine kinase for nicotine-induced Ca2+ response. J Immunol 179(5):2889–2898

    Article  CAS  PubMed  Google Scholar 

  • Rollema H, Hurst RS (2018) The contribution of agonist and antagonist activities of α4β2∗ nAChR ligands to smoking cessation efficacy: a quantitative analysis of literature data. Psychopharmacology (Berl) 235(9):2479–2505

    Article  CAS  Google Scholar 

  • Rollema H, Bertrand D Hurst R (2014) Nicotinic agonists and antagonists. Encyclopedia of psychopharmacology, vol 16(6), Springer, Heidelberg, pp 733–742

    Google Scholar 

  • Rollema H, Bertrand D, Hurst R (2015) Nicotinic agonists and antagonists. In: Stolerman IP, Price LH (eds) Encyclopedia of psychopharmacology. Springer, Berlin

    Google Scholar 

  • Roux I, Wersinger E, McIntosh JM, Fuchs PA, Glowatzki E (2011) Onset of cholinergic efferent synaptic function in sensory hair cells of the rat cochlea. J Neurosci 31(42):15092–15101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rozycka A, Dorszewska J, Steinborn B, Kempisty B, Lianeri M, Wisniewska K, Jagodzinski PP (2013) A transcript coding for a partially duplicated form of α7 nicotinic acetylcholine receptor is absent from the CD4+ T-lymphocytes of patients with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). Folia Neuropathol 51(1):65–75

    Article  CAS  PubMed  Google Scholar 

  • Scarr E (2012) Muscarinic receptors: their roles in disorders of the central nervous system and potential as therapeutic targets. CNS Neurosci Ther 18(5):369–379

    Article  CAS  PubMed  Google Scholar 

  • Schaaf CP (2014) Nicotinic acetylcholine receptors in human genetic disease. Genet Med 16(9):649–656

    Article  CAS  PubMed  Google Scholar 

  • Schubert J, Beckmann J, Hartmann S, Morhenn H-G, Szalay G, Heiss C, Schnettler R, Lips KS (2012) Expression of the non-neuronal cholinergic system in human knee synovial tissue from patients with rheumatoid arthritis and osteoarthritis. Life Sci 91(21–22):1048–1052

    Article  CAS  PubMed  Google Scholar 

  • Séguéla P, Wadiche J, Dineley-Miller K, Dani JA, Patrick JW (1993) Molecular cloning, functional properties, and distribution of rat brain alpha 7: a nicotinic cation channel highly permeable to calcium. J Neurosci 13(2):596–604

    Article  PubMed  PubMed Central  Google Scholar 

  • Sgard F, Charpantier E, Bertrand S, Walker N, Caput D, Graham D, Bertrand D, Besnard F (2002) A novel human nicotinic receptor subunit, alpha10, that confers functionality to the alpha9-subunit. Mol Pharmacol 61(1):150–159

    Article  CAS  PubMed  Google Scholar 

  • Shen W, Plotkin JL, Francardo V, Ko WK, Xie Z, Li Q, Fieblinger T, Wess J, Neubig RR, Lindsley CW, Conn PJ, Greengard P, Bezard E, Cenci MA, Surmeier DJ (2015) M4 muscarinic receptor signaling ameliorates striatal plasticity deficits in models of L-DOPA-induced dyskinesia. Neuron 88(4):762–773

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shinoe T, Matsui M, Taketo MM, Manabe T (2005) Modulation of synaptic plasticity by physiological activation of M1 muscarinic acetylcholine receptors in the mouse hippocampus. J Neurosci 25(48):11194–11200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shorey-Kendrick LE, Ford MM, Allen DC, Kuryatov A, Lindstrom J, Wilhelm L, Grant KA, Spindel ER (2015) Nicotinic receptors in non-human primates: analysis of genetic and functional conservation with humans. Neuropharmacology 96(Pt B):263–273

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sinkus ML, Graw S, Freedman R, Ross RG, Lester HA, Leonard S (2015) The human CHRNA7 and CHRFAM7A genes: a review of the genetics, regulation, and function. Neuropharmacology 96(Pt B):274–288

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stauderman KA, Mahaffy LS, Akong M, Veliçelebi G, Chavez-Noriega LE, Crona JH, Johnson EC, Elliott KJ, Gillespie A, Reid RT, Adams P, Harpold MM, Corey-Naeve J (1998) Characterization of human recombinant neuronal nicotinic acetylcholine receptor subunit combinations alpha2beta4, alpha3beta4 and alpha4beta4 stably expressed in HEK293 cells. J Pharmacol Exp Ther 284(2):777–789

    CAS  PubMed  Google Scholar 

  • Stoiljkovic M, Leventhal L, Chen A, Chen T, Driscoll R, Flood D, Hodgdon H, Hurst R, Nagy D, Piser T, Tang C, Townsend M, Tu Z, Bertrand D, Koenig G, Hajos M (2015) Concentration-response relationship of the alpha7 nicotinic acetylcholine receptor agonist FRM-17874 across multiple in vitro and in vivo assays. Biochem Pharmacol 97(4):576–589

    Article  CAS  PubMed  Google Scholar 

  • Tammimäki A, Herder P, Li P, Esch C, Laughlin JR, Akk G, Stitzel JA (2012) Impact of human D398N single nucleotide polymorphism on intracellular calcium response mediated by α3β4α5 nicotinic acetylcholine receptors. Neuropharmacology 63(6):1002–1011

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Tapia L, Kuryatov A, Lindstrom J (2007) Ca2+ permeability of the (alpha4)3(beta2)2 stoichiometry greatly exceeds that of (alpha4)2(beta2)3 human acetylcholine receptors. Mol Pharmacol 71(3):769–776

    Article  CAS  PubMed  Google Scholar 

  • Terry AV (2008) Role of the central cholinergic system in the therapeutics of schizophrenia. Curr Neuropharmacol 6(3):286–292

    Article  CAS  PubMed  Google Scholar 

  • Terry AV Jr, Callahan PM, Bertrand D (2015) R-(+) and S-(−) isomers of cotinine augment cholinergic responses in vitro and in vivo. J Pharmacol Exp Ther 352(2):405–418

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Thal DM, Sun B, Feng D, Nawaratne V, Leach K, Felder CC, Bures MG, Evans DA, Weis WI, Bachhawat P, Kobilka TS, Sexton PM, Kobilka BK, Christopoulos A (2016) Crystal structures of the M1 and M4 muscarinic acetylcholine receptors. Nature 531(7594):335–340

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Uteshev VV (2012) α7 nicotinic ACh receptors as a ligand-gated source of Ca(2+) ions: the search for a Ca(2+) optimum. Adv Exp Med Biol 740:603–638

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • van Koppen CJ, Kaiser B (2003) Regulation of muscarinic acetylcholine receptor signaling. Pharmacol Ther 98(2):197–220

    Article  PubMed  CAS  Google Scholar 

  • van Nierop P, Bertrand S, Munno DW, Gouwenberg Y, van Minnen J, Spafford JD, Syed NI, Bertrand D, Smit AB (2006) Identification and functional expression of a family of nicotinic acetylcholine receptor subunits in the central nervous system of the mollusc Lymnaea stagnalis. J Biol Chem 281(3):1680–1691

    Article  PubMed  CAS  Google Scholar 

  • Verbitsky M, Rothlin CV, Katz E, Elgoyhen AB (2000) Mixed nicotinic-muscarinic properties of the alpha9 nicotinic cholinergic receptor. Neuropharmacology 39(13):2515–2524

    Article  CAS  PubMed  Google Scholar 

  • Vernino S, Amador M, Luetje CW, Patrick J, Dani JA (1992) Calcium modulation and high calcium permeability of neuronal nicotinic acetylcholine receptors. Neuron 8(1):127–134

    Article  CAS  PubMed  Google Scholar 

  • Vibat CR, Lasalde JA, McNamee MG, Ochoa EL (1995) Differential desensitization properties of rat neuronal nicotinic acetylcholine receptor subunit combinations expressed in Xenopus laevis oocytes. Cell Mol Neurobiol 15(4):411–425

    Article  CAS  PubMed  Google Scholar 

  • Villiger Y, Szanto I, Jaconi S, Blanchet C, Buisson B, Krause KH, Bertrand D, Romand JA (2002) Expression of an alpha7 duplicate nicotinic acetylcholine receptor-related protein in human leukocytes. J Neuroimmunol 126(1–2):86–98

    Article  CAS  PubMed  Google Scholar 

  • Volpicelli LA, Levey AI (2004) Muscarinic acetylcholine receptor subtypes in cerebral cortex and hippocampus. In: Acetylcholine in the cerebral cortex. Elsevier, Amsterdam, pp 59–66

    Chapter  Google Scholar 

  • Wallace TL, Bertrand D (2013a) Alpha7 neuronal nicotinic receptors as a drug target in schizophrenia. Expert Opin Ther Targets 17(2):139–155

    Article  CAS  PubMed  Google Scholar 

  • Wallace TL, Bertrand D (2013b) Importance of the nicotinic acetylcholine receptor system in the prefrontal cortex. Biochem Pharmacol 85(12):1713–1720

    Article  CAS  PubMed  Google Scholar 

  • Walsh RM Jr, Roh SH, Gharpure A, Morales-Perez CL, Teng J, Hibbs RE (2018) Structural principles of distinct assemblies of the human alpha4beta2 nicotinic receptor. Nature 557(7704):261–265

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang H, Yu M, Ochani M, Amella CA, Tanovic M, Susarla S, Li JH, Wang H, Yang H, Ulloa L, Al-Abed Y, Czura CJ, Tracey KJ (2003) Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. Nature 421(6921):384–388

    Article  CAS  PubMed  Google Scholar 

  • Wang X-J, Liu Y-F, Wang Q-Y, Tsuruoka M, Ohta K, Wu S-X, Yakushiji M, Inoue T (2010) Functional expression of alpha 7 nicotinic acetylcholine receptors in human periodontal ligament fibroblasts and rat periodontal tissues. Cell Tissue Res 340(2):347–355

    Article  CAS  PubMed  Google Scholar 

  • Wess J, Eglen RM, Gautam D (2007) Muscarinic acetylcholine receptors: mutant mice provide new insights for drug development. Nat Rev Drug Discov 6(9):721–733

    Article  CAS  PubMed  Google Scholar 

  • Wessler I, Kirkpatrick CJ (2008) Acetylcholine beyond neurons: the non-neuronal cholinergic system in humans. Br J Pharmacol 154(8):1558–1571

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Williams NM, Franke B, Mick E, Anney RJL, Freitag CM, Gill M, Thapar A, O'Donovan MC, Owen MJ, Holmans P, Kent L, Middleton F, Zhang-James Y, Liu L, Meyer J, Nguyen TT, Romanos J, Romanos M, Seitz C, Renner TJ, Walitza S, Warnke A, Palmason H, Buitelaar J, Rommelse N, Vasquez AA, Hawi Z, Langley K, Sergeant J, Steinhausen H-C, Roeyers H, Biederman J, Zaharieva I, Hakonarson H, Elia J, Lionel AC, Crosbie J, Marshall CR, Schachar R, Scherer SW, Todorov A, Smalley SL, Loo S, Nelson S, Shtir C, Asherson P, Reif A, Lesch K-P, Faraone SV (2012) Genome-wide analysis of copy number variants in attention deficit hyperactivity disorder: the role of rare variants and duplications at 15q13.3. Am J Psychiatry 169(2):195–204

    Article  PubMed  PubMed Central  Google Scholar 

  • Zaninetti M, Tribollet E, Bertrand D, Raggenbass M (1999) Presence of functional neuronal nicotinic acetylcholine receptors in brainstem motoneurons of the rat. Eur J Neurosci 11(8):2737–2748

    Article  CAS  PubMed  Google Scholar 

  • Zhou Y, Nelson ME, Kuryatov A, Choi C, Cooper J, Lindstrom J (2003) Human alpha4beta2 acetylcholine receptors formed from linked subunits. J Neurosci 23(27):9004–9015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zwart R, Vijverberg HP (1998) Four pharmacologically distinct subtypes of alpha4beta2 nicotinic acetylcholine receptor expressed in Xenopus laevis oocytes. Mol Pharmacol 54(6):1124–1131

    Article  CAS  PubMed  Google Scholar 

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  1. HiQScreen Sàrl, Geneva, Switzerland

    Daniel Bertrand

  2. BlackThorn Therapeutics, San Francisco, CA, USA

    Tanya L. Wallace

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    Mohammed Shoaib

  2. BlackThorn Therapeutics, San Francisco, CA, USA

    Tanya L. Wallace

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Bertrand, D., Wallace, T.L. (2020). A Review of the Cholinergic System and Therapeutic Approaches to Treat Brain Disorders. In: Shoaib, M., Wallace, T. (eds) Behavioral Pharmacology of the Cholinergic System. Current Topics in Behavioral Neurosciences, vol 45. Springer, Cham. https://doi.org/10.1007/7854_2020_141

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