Alpha-7 nicotinic receptor

Molecular model of the α7 nicotinic receptor.

The alpha-7 nicotinic receptor, also known as the α7 receptor, is a type of nicotinic acetylcholine receptor implicated in long term memory, consisting entirely of α7 subunits.[1] As with other nicotinic acetylcholine receptors, functional α7 receptors are pentameric [i.e., (α7)5 stoichiometry].

It is located in the brain, spleen, and lymphocytes of lymph nodes where activation yields post- and presynaptic excitation,[1] mainly by increased Ca2+ permeability.

Medical relevance

Recent work has demonstrated a potential role in reducing inflammatory neurotoxicity in stroke, myocardial infarction, sepsis, and alzheimers disease.[2][3][4]

An α7 nicotinic agonist appears to have positive effects on neurocognition in persons with schizophrenia.[5]

Both α4β2 and α7 nicotinic receptors appear to be critical for memory, working memory, learning, and attention.[6]

α7-nicotinic receptors also appear to be involved in cancer progression. They have been shown to mediate cancer cell proliferation and metastasis.[7] α7 receptors are also involved in angiogenic activity, and have anti-apoptotic effects.[8][9]

Ligands

Agonists

Positive Allosteric Modulators (PAMs)

At least two types of positive allosteric modulators (PAMs) can be distinguished.[23]

Other

Antagonists

It is found that anandamide and ethanol cause an additive inhibition on the function of α7-receptor by interacting with distinct regions of the receptor. Although ethanol inhibition of the α7-receptor is likely to involve the N-terminal region of the receptor, the site of action for anandamide is located in the transmembrane and carboxyl-terminal domains of the receptors.[32]

See also

References

  1. 1 2 Pharmacology, (Rang, Dale, Ritter & Moore, ISBN 0-443-07145-4, 5th ed., Churchill Livingstone 2003) p. 138.
  2. ↑ Rosas-Ballina, M.; Olofsson, P. S.; Ochani, M.; Valdes-Ferrer, S. I.; Levine, Y. A.; Reardon, C.; Tusche, M. W.; Pavlov, V. A.; Andersson, U. (2011). "Acetylcholine-Synthesizing T Cells Relay Neural Signals in a Vagus Nerve Circuit". Science. 334 (6052): 98–101. doi:10.1126/science.1209985. PMID 21921156.
  3. ↑ Tracey, KJ (2007). "Physiology and immunology of the cholinergic antiinflammatory pathway". The Journal of Clinical Investigation. 117 (2): 289–96. doi:10.1172/JCI30555. PMC 1783813Freely accessible. PMID 17273548.
  4. ↑ Norman, G. J.; Morris, J. S.; Karelina, K.; Weil, Z. M.; Zhang, N.; Al-Abed, Y.; Brothers, H. M.; Wenk, G. L.; Pavlov, V. A. (2011). "Cardiopulmonary Arrest and Resuscitation Disrupts Cholinergic Anti-Inflammatory Processes: A Role for Cholinergic 7 Nicotinic Receptors". Journal of Neuroscience. 31 (9): 3446–52. doi:10.1523/JNEUROSCI.4558-10.2011. PMID 21368056.
  5. ↑ Olincy, A; Harris, JG; Johnson, LL; Pender, V; Kongs, S; Allensworth, D; Ellis, J; Zerbe, GO; Leonard, S (2006). "Proof-of-concept trial of an alpha7 nicotinic agonist in schizophrenia". Arch Gen Psychiatry. 63 (6): 630–638. doi:10.1001/archpsyc.63.6.630. PMID 16754836.
  6. ↑ Levin, E. D.; McClernon, F. J.; Rezvani, A. H. (2005). "Nicotinic effects on cognitive function: Behavioral characterization, pharmacological specification, and anatomic localization". Psychopharmacology. 184 (3–4): 523–539. doi:10.1007/s00213-005-0164-7. PMID 16220335.
  7. ↑ Dasgupta, P; Rizwani, W; Pillai, S; Kinkade, R; Kovacs, M; Rastogi, S; Banerjee, S; Carless, M; Kim, E; Coppola, D; Haura, E; Chellappan, S (2009). "Nicotine induces cell proliferation, invasion and epithelial-mesenchymal transition in a variety of human cancer cell lines". International Journal of Cancer. Journal International Du Cancer. 124 (1): 36–45. doi:10.1002/ijc.23894. PMC 2826200Freely accessible. PMID 18844224.
  8. ↑ Brown, K. C.; Lau, J. K.; Dom, A. M.; Witte, T. R.; Luo, H; Crabtree, C. M.; Shah, Y. H.; Shiflett, B. S.; Marcelo, A. J.; Proper, N. A.; Hardman, W. E.; Egleton, R. D.; Chen, Y. C.; Mangiarua, E. I.; Dasgupta, P (2012). "MG624, an α7-nAChR antagonist, inhibits angiogenesis via the Egr-1/FGF2 pathway". Angiogenesis. 15 (1): 99–114. doi:10.1007/s10456-011-9246-9. PMID 22198237.
  9. ↑ Gergalova, G; Lykhmus, O; Kalashnyk, O; Koval, L; Chernyshov, V; Kryukova, E; Tsetlin, V; Komisarenko, S; Skok, M (2012). "Mitochondria express α7 nicotinic acetylcholine receptors to regulate Ca2+ accumulation and cytochrome c release: Study on isolated mitochondria". PLOS ONE. 7 (2): e31361. doi:10.1371/journal.pone.0031361. PMC 3281078Freely accessible. PMID 22359587.
  10. ↑ Mazurov A, Klucik J, Miao L, et al. (2005). "2-(Arylmethyl)-3-substituted quinuclidines as selective alpha 7 nicotinic receptor ligands". Bioorg. Med. Chem. Lett. 15 (8): 2073–7. doi:10.1016/j.bmcl.2005.02.045. PMID 15808471.
  11. ↑ Tietje KR, Anderson DJ, Bitner RS, et al. (2008). "Preclinical characterization of A-582941: a novel alpha7 neuronal nicotinic receptor agonist with broad spectrum cognition-enhancing properties". CNS Neurosci Ther. 14 (1): 65–82. doi:10.1111/j.1527-3458.2008.00037.x. PMID 18482100.
  12. ↑ Talantova, M.; Sanz-Blasco, S.; Zhang, X.; Xia, P.; Akhtar, M. W.; Okamoto, S. -I.; Dziewczapolski, G.; Nakamura, T.; Cao, G.; Pratt, A. E.; Kang, Y. -J.; Tu, S.; Molokanova, E.; McKercher, S. R.; Hires, S. A.; Sason, H.; Stouffer, D. G.; Buczynski, M. W.; Solomon, J. P.; Michael, S.; Powers, E. T.; Kelly, J. W.; Roberts, A.; Tong, G.; Fang-Newmeyer, T.; Parker, J.; Holland, E. A.; Zhang, D.; Nakanishi, N.; Chen, H. -S. V. (2013). "Aβ induces astrocytic glutamate release, extrasynaptic NMDA receptor activation, and synaptic loss". Proceedings of the National Academy of Sciences. 110 (27): E2518. doi:10.1073/pnas.1306832110. PMC 3704025Freely accessible. PMID 23776240.
  13. ↑ Marrero MB, Papke RL, Bhatti BS, Shaw S, Bencherif M (2004). "The neuroprotective effect of 2-(3-pyridyl)-1-azabicyclo[3.2.2]nonane (TC-1698), a novel alpha7 ligand, is prevented through angiotensin II activation of a tyrosine phosphatase". J. Pharmacol. Exp. Ther. 309 (1): 16–27. doi:10.1124/jpet.103.061655. PMID 14722323.
  14. ↑ Preskorn, S. H.; Gawryl, M.; Dgetluck, N.; Palfreyman, M.; Bauer, L. O.; Hilt, D. C. (2014). "Normalizing Effects of EVP-6124, an Alpha-7 Nicotinic Partial Agonist, on Event-Related Potentials and Cognition". Journal of Psychiatric Practice. 20 (1): 12–24. doi:10.1097/01.pra.0000442935.15833.c5. PMID 24419307.
  15. ↑ http://envivopharma.com/pdf/EVP-6124AAICPressConf.pdf
  16. 1 2 Sadigh-Eteghad S, Talebi M, Mahmoudi J, Babri S, Shanehbandi D (2015). "Selective activation of α 7 nicotinic acetylcholine receptor by PHA-543613 improves Aβ 25–35-mediated cognitive deficits in mice". Neuroscience. 298: 81–93. doi:10.1016/j.neuroscience.2015.04.017. PMID 25881725.
  17. ↑ Acker BA, Jacobsen EJ, Rogers BN, et al. (2008). "Discovery of N-[(3R,5R)-1-azabicyclo[3.2.1]oct-3-yl] furo[2,3-c]pyridine-5-carboxamide as an agonist of the alpha7 nicotinic acetylcholine receptor: in vitro and in vivo activity". Bioorg. Med. Chem. Lett. 18 (12): 3611–5. doi:10.1016/j.bmcl.2008.04.070. PMID 18490160.
  18. ↑ Walker DP, Wishka DG, Piotrowski DW, et al. (2006). "Design, synthesis, structure-activity relationship, and in vivo activity of azabicyclic aryl amides as alpha7 nicotinic acetylcholine receptor agonists". Bioorg. Med. Chem. 14 (24): 8219–48. doi:10.1016/j.bmc.2006.09.019. PMID 17011782.
  19. ↑ Biton B, Bergis OE, Galli F, et al. (2007). "SSR180711, a novel selective alpha7 nicotinic receptor partial agonist: (1) binding and functional profile". Neuropsychopharmacology. 32 (1): 1–16. doi:10.1038/sj.npp.1301189. PMID 17019409.
  20. ↑ Macor JE, Gurley D, Lanthorn T, et al. (2001). "The 5-HT3 antagonist tropisetron (ICS 205-930) is a potent and selective alpha7 nicotinic receptor partial agonist". Bioorg. Med. Chem. Lett. 11 (3): 319–21. doi:10.1016/S0960-894X(00)00670-3. PMID 11212100.
  21. ↑ https://isccb12.webs.ull.es/PDF-Final/38-Rubio.pdf
  22. ↑ Dallanoce C, Magrone P, Matera C, Frigerio F, Grazioso G, De Amici M, Fucile S, Piccari V, Frydenvang K, Pucci L, Gotti C, Clementi F, De Micheli C (2011). "Design, Synthesis, and Pharmacological Characterization of Novel Spirocyclic Quinuclidinyl-Δ2-Isoxazoline Derivatives as Potent and Selective Agonists of α7 Nicotinic Acetylcholine Receptors". ChemMedChem. 6 (5): 889–903. doi:10.1002/cmdc.201000514. PMID 21365765.
  23. ↑ Grønlien JH, Håkerud M, Ween H, et al. (2007). "Distinct profiles of alpha7 nAChR positive allosteric modulation revealed by structurally diverse chemotypes". Mol. Pharmacol. 72 (3): 715–24. doi:10.1124/mol.107.035410. PMID 17565004.
  24. ↑ Hurst RS, Hajós M, Raggenbass M, et al. (2005). "A novel positive allosteric modulator of the alpha7 neuronal nicotinic acetylcholine receptor: in vitro and in vivo characterization". J. Neurosci. 25 (17): 4396–405. doi:10.1523/JNEUROSCI.5269-04.2005. PMID 15858066.
  25. ↑ Timmermann DB, Grønlien JH, Kohlhaas KL, et al. (2007). "An allosteric modulator of the alpha7 nicotinic acetylcholine receptor possessing cognition-enhancing properties in vivo". J. Pharmacol. Exp. Ther. 323 (1): 294–307. doi:10.1124/jpet.107.120436. PMID 17625074.
  26. ↑ Ng, HJ; et al. (2007). "Nootropic α7 nicotinic receptor allosteric modulator derived from GABA A receptor modulators". PNAS. 104 (19): 8059–8064. doi:10.1073/pnas.0701321104. PMC 1876571Freely accessible. PMID 17470817.
  27. ↑ Faghih R, Gopalakrishnan SM, Gronlien JH, et al. (May 2009). "Discovery of 4-(5-(4-chlorophenyl)-2-methyl-3-propionyl-1H-pyrrol-1-yl)benzenesulfonamide (A-867744) as a novel positive allosteric modulator of the alpha7 nicotinic acetylcholine receptor". J. Med. Chem. 52 (10): 3377–84. doi:10.1021/jm9003818. PMID 19419141.
  28. ↑ Malysz J, Gronlien JH, Anderson DJ, et al. (April 2009). "In vitro pharmacological characterization of a novel allosteric modulator of {alpha}7 nAChR, A-867744, exhibiting unique pharmacological profile". J. Pharmacol. Exp. Ther. 330 (1): 257–67. doi:10.1124/jpet.109.151886. PMID 19389923.
  29. ↑ "The anti-dementia drug nefiracetam facilitates hippocampal synaptic transmission by functionally targeting presynaptic nicotinic ACh receptors". Brain Res Mol Brain Res. 80: 53–62. Aug 2000. PMID 11039729.
  30. ↑ "Nootropic drug modulation of neuronal nicotinic acetylcholine receptors in rat cortical neurons". Mol Pharmacol. 59: 674–83. Apr 2001. PMID 11259610.
  31. ↑ "Presynaptic nicotinic acetylcholine receptors as a functional target of nefiracetam in inducing a long-lasting facilitation of hippocampal neurotransmission". Alzheimer Dis Assoc Disord. 14 Suppl 1: S82–94. 2000. doi:10.1097/00002093-200000001-00013. PMID 10850735.
  32. ↑ Oz, Murat; Jackson, Shelley N.; Woods, Amina S.; Morales, Marisela; Zhang, Li (2005-06-01). "Additive Effects of Endogenous Cannabinoid Anandamide and Ethanol on α7-Nicotinic Acetylcholine Receptor-Mediated Responses in Xenopus Oocytes". Journal of Pharmacology and Experimental Therapeutics. 313 (3): 1272–1280. doi:10.1124/jpet.104.081315. ISSN 0022-3565.
  33. ↑ Whiteaker P, Christensen S, Yoshikami D, et al. (2007). "Discovery, synthesis, and structure activity of a highly selective α7 nicotinic acetylcholine receptor antagonist". Biochemistry. 46 (22): 6628–38. doi:10.1021/bi7004202. PMID 17497892.
  34. ↑ Tsuneki H, You Y, Toyooka N, et al. (2004). "Alkaloids indolizidine 235B', quinolizidine 1-epi-207I, and the tricyclic 205B are potent and selective noncompetitive inhibitors of nicotinic acetylcholine receptors". Mol. Pharmacol. 66 (4): 1061–9. doi:10.1124/mol.104.000729. PMID 15258256.
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