Alpha-7 nicotinic receptor

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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.

Further, recent work has implicated this receptor as being important for generation of adult mammal neurons in the retina.[2]

Medical relevance[edit]

Recent work has demonstrated a potential role in reducing inflammatory neurotoxicity in stroke, myocardial infarction, sepsis, and alzheimers disease.[3][4][5]

An α7 nicotinic agonist appears to have positive effects on neurocognition in persons with schizophrenia.[6]

Both α4β2 and α7 nicotinic receptors appear to be critical for memory, working memory, learning, and attention.[7]

α7-nicotinic receptors also appear to be involved in cancer progression. They have been shown to mediate cancer cell proliferation and metastasis.[8] α7 receptors are also involved in angiogenic and neurogenic activity, and have anti-apoptotic effects.[9][10][11]

Ligands[edit]

Agonists[edit]

Positive Allosteric Modulators (PAMs)[edit]

At least two types of positive allosteric modulators (PAMs) can be distinguished.[26]

  • PNU-120,596[27]
  • NS-1738: marginal effects on α7 desensitization kinetics; modestly brain-penetrant[28]
  • AVL-3288: unlike the above PAMs, AVL-3288 does not affect α7 desensitization kinetics, and is readily brain penetrant. Improves cognitive behavior in animal models[29] In clinical development for cognitive deficits in schizophrenia.
  • A-867744[30][31]
  • Ivermectin
  • Galantamine

Other[edit]

Antagonists[edit]

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.[35]

See also[edit]

References[edit]

  1. ^ a b Pharmacology, (Rang, Dale, Ritter & Moore, ISBN 0-443-07145-4, 5th ed., Churchill Livingstone 2003) p. 138.
  2. ^ Webster, Mark K.; Cooley-Themm, Cynthia A.; Barnett, Joseph D.; Bach, Harrison B.; Vainner, Jessica M.; Webster, Sarah E.; Linn, Cindy L. (2017-03-27). "Evidence of BrdU-positive retinal neurons after application of an Alpha7 nicotinic acetylcholine receptor agonist". Neuroscience. 346: 437–446. ISSN 1873-7544. PMC 5341387Freely accessible. PMID 28147247. doi:10.1016/j.neuroscience.2017.01.029. 
  3. ^ 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. PMID 21921156. doi:10.1126/science.1209985. 
  4. ^ Tracey, KJ (2007). "Physiology and immunology of the cholinergic antiinflammatory pathway". The Journal of Clinical Investigation. 117 (2): 289–96. PMC 1783813Freely accessible. PMID 17273548. doi:10.1172/JCI30555. 
  5. ^ 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. PMID 21368056. doi:10.1523/JNEUROSCI.4558-10.2011. 
  6. ^ 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. PMID 16754836. doi:10.1001/archpsyc.63.6.630. 
  7. ^ 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. PMID 16220335. doi:10.1007/s00213-005-0164-7. 
  8. ^ 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. PMC 2826200Freely accessible. PMID 18844224. doi:10.1002/ijc.23894. 
  9. ^ 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. PMID 22198237. doi:10.1007/s10456-011-9246-9. 
  10. ^ Wang J, Lu Z, Fu X, Zhang D, Yu L, Li N, Gao Y, Liu X, Yin C, Ke J, Li L, Zhai M, Wu S, Fan J, Lv L, Liu J, Chen X, Yang Q, Wang J (May 2017). "Alpha-7 Nicotinic Receptor Signaling Pathway Participates in the Neurogenesis Induced by ChAT-Positive Neurons in the Subventricular Zone". Transl Stroke Res. PMID 28551702. doi:10.1007/s12975-017-0541-7. 
  11. ^ 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. PMC 3281078Freely accessible. PMID 22359587. doi:10.1371/journal.pone.0031361. 
  12. ^ 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. PMID 15808471. doi:10.1016/j.bmcl.2005.02.045. 
  13. ^ 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. PMID 18482100. doi:10.1111/j.1527-3458.2008.00037.x. 
  14. ^ 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. PMC 3704025Freely accessible. PMID 23776240. doi:10.1073/pnas.1306832110. 
  15. ^ 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. PMID 14722323. doi:10.1124/jpet.103.061655. 
  16. ^ 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. PMID 24419307. doi:10.1097/01.pra.0000442935.15833.c5. 
  17. ^ http://envivopharma.com/pdf/EVP-6124AAICPressConf.pdf
  18. ^ a b 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. PMID 25881725. doi:10.1016/j.neuroscience.2015.04.017. 
  19. ^ 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. PMID 18490160. doi:10.1016/j.bmcl.2008.04.070. 
  20. ^ 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. PMID 17011782. doi:10.1016/j.bmc.2006.09.019. 
  21. ^ 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. PMID 17019409. doi:10.1038/sj.npp.1301189. 
  22. ^ 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. PMID 11212100. doi:10.1016/S0960-894X(00)00670-3. 
  23. ^ Dallanoce, Clelia; Matera, Carlo; Amici, Marco De; Rizzi, Luca; Pucci, Luca; Gotti, Cecilia; Clementi, Francesco; Micheli, Carlo De (2012-07-01). "The enantiomers of epiboxidine and of two related analogs: Synthesis and estimation of their binding affinity at α4β2 and α7 neuronal nicotinic acetylcholine receptors". Chirality. 24 (7): 543–551. ISSN 1520-636X. doi:10.1002/chir.22052. 
  24. ^ https://isccb12.webs.ull.es/PDF-Final/38-Rubio.pdf
  25. ^ 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. PMID 21365765. doi:10.1002/cmdc.201000514. 
  26. ^ 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. PMID 17565004. doi:10.1124/mol.107.035410. 
  27. ^ 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. PMID 15858066. doi:10.1523/JNEUROSCI.5269-04.2005. 
  28. ^ 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. PMID 17625074. doi:10.1124/jpet.107.120436. 
  29. ^ Ng, HJ; et al. (2007). "Nootropic α7 nicotinic receptor allosteric modulator derived from GABA A receptor modulators". PNAS. 104 (19): 8059–8064. PMC 1876571Freely accessible. PMID 17470817. doi:10.1073/pnas.0701321104. 
  30. ^ 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. PMID 19419141. doi:10.1021/jm9003818. 
  31. ^ 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. PMID 19389923. doi:10.1124/jpet.109.151886. 
  32. ^ "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. 
  33. ^ "Nootropic drug modulation of neuronal nicotinic acetylcholine receptors in rat cortical neurons". Mol Pharmacol. 59: 674–83. Apr 2001. PMID 11259610. 
  34. ^ "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. PMID 10850735. doi:10.1097/00002093-200000001-00013. 
  35. ^ 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. ISSN 0022-3565. doi:10.1124/jpet.104.081315. 
  36. ^ 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. PMID 17497892. doi:10.1021/bi7004202. 
  37. ^ 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. PMID 15258256. doi:10.1124/mol.104.000729.