Alpha-3 beta-4 nicotinic receptor explained

The alpha-3 beta-4 nicotinic receptor, also known as the α3β4 receptor and the ganglion-type nicotinic receptor,[1] is a type of nicotinic acetylcholine receptor, consisting of α3 and β4 subunits.[2] [3] It is located in the autonomic ganglia[4] and adrenal medulla,[5] where activation yields post- and/or presynaptic excitation, mainly by increased Na+ and K+ permeability.

As with other nicotinic acetylcholine receptors, the α3β4 receptor is pentameric [(α3)<sub>m</sub>(β4)<sub>n</sub> where m + n = 5]. The exact subunit stoichiometry is not known and it is possible that more than one functional α3β4 receptor assembles in vivo with varying subunit stoichiometries.

Ligands which inhibit the α3β4 receptor have been shown to modulate drug-seeking behavior,[6] making α3β4 a promising target for the development of novel antiaddictive agents.

Ligands

Source:[7]

Agonists

Antagonists

Competitive

Noncompetitive

See also

Notes and References

  1. Pharmacology, (Rang, Dale, Ritter & Moore,, 5th ed., Churchill Livingstone 2003) p. 138.
  2. 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 . Characterization of human recombinant neuronal nicotinic acetylcholine receptor subunit combinations alpha2beta4, alpha3beta4 and alpha4beta4 stably expressed in HEK293 cells . The Journal of Pharmacology and Experimental Therapeutics . 284 . 2 . 777–89 . February 1998 . 9454827 .
  3. Xiao Y, Kellar KJ . The comparative pharmacology and up-regulation of rat neuronal nicotinic receptor subtype binding sites stably expressed in transfected mammalian cells . The Journal of Pharmacology and Experimental Therapeutics . 310 . 1 . 98–107 . July 2004 . 15016836 . 10.1124/jpet.104.066787 . 23900581 .
  4. Poth K, Nutter TJ, Cuevas J, Parker MJ, Adams DJ, Luetje CW . Heterogeneity of nicotinic receptor class and subunit mRNA expression among individual parasympathetic neurons from rat intracardiac ganglia . The Journal of Neuroscience . 17 . 2 . 586–96 . January 1997 . 8987781 . US National Library of Medicine . 10.1523/JNEUROSCI.17-02-00586.1997 . 6573231 . free .
  5. Gotti C, Clementi F, Fornari A, Gaimarri A, Guiducci S, Manfredi I, Moretti M, Pedrazzi P, Pucci L, Zoli M . Structural and functional diversity of native brain neuronal nicotinic receptors . Biochemical Pharmacology . 78 . 7 . 703–11 . October 2009 . 19481063 . 10.1016/j.bcp.2009.05.024 . US National Library of Medicine .
  6. HarringtonEtAl . L. . Role of β4* Nicotinic Acetylcholine Receptors in the Habenulo–Interpeduncular Pathway in Nicotine Reinforcement in Mice . Neuropsychopharmacology . 2015 . 41 . 7 . 1790–1802 . 10.1038/npp.2015.346 . 26585290 . 4869047 .
  7. Matera . Carlo . Papotto . Claudio . Dallanoce . Clelia . De Amici . Marco . 2023-08-01 . Advances in small molecule selective ligands for heteromeric nicotinic acetylcholine receptors . Pharmacological Research . 194 . 106813 . 10.1016/j.phrs.2023.106813 . 1043-6618. free . 37302724 . 2434/978688 . free .
  8. Xiao Y, Meyer EL, Thompson JM, Surin A, Wroblewski J, Kellar KJ . Rat alpha3/beta4 subtype of neuronal nicotinic acetylcholine receptor stably expressed in a transfected cell line: pharmacology of ligand binding and function . Molecular Pharmacology . 54 . 2 . 322–33 . August 1998 . 9687574 . 10.1124/mol.54.2.322.
  9. Matera C, Quadri M, Sciaccaluga M, Pomè DY, Fasoli F, De Amici M, Fucile S, Gotti C, Dallanoce C, Grazioso G . Modification of the anabaseine pyridine nucleus allows achieving binding and functional selectivity for the α3β4 nicotinic acetylcholine receptor subtype . European Journal of Medicinal Chemistry . 108 . 392–405 . January 2016 . 26706350 . 10.1016/j.ejmech.2015.11.045 . 2434/352478 . free .
  10. Prado WA, Segalla DK . 2004 . Antinociceptive effects of bethanechol or dimethylphenylpiperazinium in models of phasic or incisional pain in rats . Brain Res . 1018 . 2. 272–82 . 10.1016/j.brainres.2004.05.085 . 15276888 . 45145197 .
  11. Page 149
  12. Bencherif M, Schmitt JD, Bhatti BS, Crooks P, Caldwell WS, Lovette ME, Fowler K, Reeves L, Lippiello PM . The heterocyclic substituted pyridine derivative (+/-)-2-(-3-pyridinyl)-1-azabicyclo[2.2.2]octane (RJR-2429): a selective ligand at nicotinic acetylcholine receptors . The Journal of Pharmacology and Experimental Therapeutics . 284 . 3 . 886–94 . March 1998 . 9495846 .
  13. Web site: SR 16584 (CAS 1150153-86-8). R&D Systems. 3 December 2017.
  14. Zaveri. NT. The nociceptin/orphanin FQ receptor (NOP) as a target for drug abuse medications.. Current Topics in Medicinal Chemistry. 2011. 11. 9. 1151–6. 10.2174/156802611795371341. 21050175. 3899399.
  15. Hernandez SC, Bertolino M, Xiao Y, Pringle KE, Caruso FS, Kellar KJ . Dextromethorphan and its metabolite dextrorphan block alpha3beta4 neuronal nicotinic receptors . The Journal of Pharmacology and Experimental Therapeutics . 293 . 3 . 962–7 . June 2000 . 10869398 .
  16. Damaj MI, Flood P, Ho KK, May EL, Martin BR . Effect of dextrometorphan and dextrorphan on nicotine and neuronal nicotinic receptors: in vitro and in vivo selectivity . The Journal of Pharmacology and Experimental Therapeutics . 312 . 2 . 780–5 . February 2005 . 15356218 . 10.1124/jpet.104.075093 . 149958 .
  17. Blockade of Rat α3β4 Nicotinic Receptor Function by Methadone, Its Metabolites, and Structural Analogs — JPET . Journal of Pharmacology and Experimental Therapeutics . October 2001 . 299 . 1 . 366–371 . Xiao . Yingxian . Smith . Richard D. . Caruso . Frank S. . Kellar . Kenneth J. .
  18. Arias HR, Targowska-Duda KM, Feuerbach D, Sullivan CJ, Maciejewski R, Jozwiak K . Different interaction between tricyclic antidepressants and mecamylamine with the human alpha3beta4 nicotinic acetylcholine receptor ion channel . Neurochemistry International . 56 . 4 . 642–9 . March 2010 . 20117161 . 10.1016/j.neuint.2010.01.011 . 29461221 .
  19. Miller DK, Wong EH, Chesnut MD, Dwoskin LP . Reboxetine: functional inhibition of monoamine transporters and nicotinic acetylcholine receptors . The Journal of Pharmacology and Experimental Therapeutics . 302 . 2 . 687–95 . August 2002 . 12130733 . 10.1124/jpet.302.2.687 .
  20. Toll L, Zaveri NT, Polgar WE, Jiang F, Khroyan TV, Zhou W, Xie XS, Stauber GB, Costello MR, Leslie FM . AT-1001: a high affinity and selective α3β4 nicotinic acetylcholine receptor antagonist blocks nicotine self-administration in rats . Neuropsychopharmacology . 37 . 6 . 1367–76 . May 2012 . 22278092 . 3327842 . 10.1038/npp.2011.322 .
  21. Book: Borges R, Gandía L . González-Rubioa JM, Rojoa J, Tapiaa L, Maneud V, Muletc J, Valorc LM, Criadoc M, Salac F, García AG, Gandía L . Choline as a tool to evaluate nicotinic receptor function in chromaffin cells . Cell Biology of the Chromaffin Cell . Instituto Teófilo Hernando . Spain . 2004 . https://isccb12.webs.ull.es/PDF-Final/38-Rubio.pdf .

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