Galanin receptor

Last updated
galanin receptor 1
Identifiers
SymbolGALR1
Alt. symbolsGALNR1, GALNR
NCBI gene 2587
HGNC 4132
OMIM 600377
RefSeq NM_001480
UniProt P47211
Other data
Locus Chr. 18 q23
Search for
Structures Swiss-model
Domains InterPro
galanin receptor 2
Identifiers
SymbolGALR2
NCBI gene 8811
HGNC 4133
OMIM 603691
RefSeq NM_003857
UniProt O43603
Other data
Locus Chr. 17 q25.3
Search for
Structures Swiss-model
Domains InterPro
galanin receptor 3
Identifiers
SymbolGALR3
NCBI gene 8484
HGNC 4134
OMIM 603692
RefSeq NM_003614
UniProt O60755
Other data
Locus Chr. 22 q12.2-13.1
Search for
Structures Swiss-model
Domains InterPro

The galanin receptor is a G protein-coupled receptor, or metabotropic receptor which binds galanin. [1]

Contents

Galanin receptors can be found throughout the peripheral and central nervous systems and the endocrine system. So far three subtypes are known to exist: GAL-R1, GAL-R2, and GAL-R3. [2] The specific function of each subtype remains to be fully elucidated, although as of 2009 great progress is currently being made in this respect with the generation of receptor subtype-specific knockout mice, [3] [4] and the first selective ligands for galanin receptor subtypes. Selective galanin agonists are anticonvulsant, [5] [6] [7] while antagonists produce antidepressant and anxiolytic effects in animals, [8] [9] [10] [11] [12] so either agonist or antagonist ligands for the galanin receptors may be potentially therapeutic compounds in humans.

Ligands

Agonists

Non-selective
GAL1 selective
GAL1/2 selective
GAL2 selective

Antagonists

Non-selective
GAL1 selective
GAL2 selective
GAL3 selective

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<span class="mw-page-title-main">Galanin</span>

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Galanin receptor 1 (GAL1) is a G-protein coupled receptor encoded by the GALR1 gene.

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<span class="mw-page-title-main">Galmic</span> Chemical compound

Galmic is a drug which acts as a selective, non-peptide agonist at the galanin receptors GALR. It has anticonvulsant, antidepressant and analgesic effects in animal studies, but also inhibits memory functions.

<span class="mw-page-title-main">Galnon</span> Chemical compound

Galnon is a drug which acts as a selective, non-peptide agonist at the galanin receptors GALR. It has anticonvulsant, anxiolytic, anorectic and amnestic effects in animal studies.

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<span class="mw-page-title-main">HT-2157</span> Chemical compound

HT-2157 is a drug which acts as a selective non-peptide antagonist for the receptor GAL-3, which is usually activated by the neuropeptide galanin. Blocking this receptor with HT-2157 produced increased serotonin release, as well as producing antidepressant and anxiolytic effects in animal studies, and it was also being researched for treatment of cognitive dysfunction. All human clinical trials were terminated due to safety concerns however, and new GAL-3 antagonists are now being sought instead.

References

  1. ↑ Lang R, Gundlach AL, Kofler B (2007). "The galanin peptide family: receptor pharmacology, pleiotropic biological actions, and implications in health and disease". Pharmacol. Ther. 115 (2): 177–207. doi:10.1016/j.pharmthera.2007.05.009. PMID   17604107.
  2. ↑ Branchek TA, Smith KE, Gerald C, Walker MW (2000). "Galanin receptor subtypes". Trends Pharmacol. Sci. 21 (3): 109–17. doi:10.1016/S0165-6147(00)01446-2. PMID   10689365.
  3. ↑ Rustay NR, Wrenn CC, Kinney JW, Holmes A, Bailey KR, Sullivan TL, Harris AP, Long KC, Saavedra MC, Starosta G, Innerfield CE, Yang RJ, Dreiling JL, Crawley JN (June 2005). "Galanin impairs performance on learning and memory tasks: findings from galanin transgenic and GAL-R1 knockout mice". Neuropeptides. 39 (3): 239–43. doi:10.1016/j.npep.2004.12.026. PMID   15944016. S2CID   32791271.
  4. ↑ Lu X, Ross B, Sanchez-Alavez M, Zorrilla EP, Bartfai T (August 2008). "Phenotypic analysis of GalR2 knockout mice in anxiety- and depression-related behavioral tests". Neuropeptides. 42 (4): 387–97. doi:10.1016/j.npep.2008.04.009. PMC   3399724 . PMID   18554714.
  5. ↑ Mazarati A, Lundström L, Sollenberg U, Shin D, Langel U, Sankar R (August 2006). "Regulation of kindling epileptogenesis by hippocampal galanin type 1 and type 2 receptors: The effects of subtype-selective agonists and the role of G-protein-mediated signaling". The Journal of Pharmacology and Experimental Therapeutics. 318 (2): 700–8. doi:10.1124/jpet.106.104703. PMC   1508166 . PMID   16699066.
  6. ↑ Lerner JT, Sankar R, Mazarati AM (June 2008). "Galanin and epilepsy". Cellular and Molecular Life Sciences. 65 (12): 1864–71. doi:10.1007/s00018-008-8161-8. PMID   18500639. S2CID   38771548.
  7. ↑ Zhang L, Robertson CR, Green BR, Pruess TH, White HS, Bulaj G (February 2009). "Structural Requirements for a Lipoamino Acid in Modulating the Anticonvulsant Activities of Systemically Active Galanin Analogues". Journal of Medicinal Chemistry. 52 (5): 1310–6. doi:10.1021/jm801397w. PMC   2765488 . PMID   19199479.
  8. ↑ Lu X, Barr AM, Kinney JW, Sanna P, Conti B, Behrens MM, Bartfai T (January 2005). "A role for galanin in antidepressant actions with a focus on the dorsal raphe nucleus". Proceedings of the National Academy of Sciences of the United States of America. 102 (3): 874–9. Bibcode:2005PNAS..102..874L. doi: 10.1073/pnas.0408891102 . PMC   545581 . PMID   15647369.
  9. ↑ Barr AM, Kinney JW, Hill MN, Lu X, Biros S, Rebek J, Bartfai T (September 2006). "A novel, systemically active, selective galanin receptor type-3 ligand exhibits antidepressant-like activity in preclinical tests". Neuroscience Letters. 405 (1–2): 111–5. doi:10.1016/j.neulet.2006.06.033. PMID   16854525. S2CID   39707220.
  10. ↑ Lu X, Sharkey L, Bartfai T (June 2007). "The brain galanin receptors: targets for novel antidepressant drugs". CNS & Neurological Disorders Drug Targets. 6 (3): 183–92. doi:10.2174/187152707780619335. PMID   17511615.
  11. ↑ Kuteeva E, Hökfelt T, Wardi T, Ogren SO (June 2008). "Galanin, galanin receptor subtypes and depression-like behaviour". Cellular and Molecular Life Sciences. 65 (12): 1854–63. doi:10.1007/s00018-008-8160-9. PMID   18500640. S2CID   27882520.
  12. ↑ Kuteeva E, Wardi T, Lundström L, Sollenberg U, Langel U, Hökfelt T, Ogren SO (October 2008). "Differential role of galanin receptors in the regulation of depression-like behavior and monoamine/stress-related genes at the cell body level". Neuropsychopharmacology. 33 (11): 2573–85. doi:10.1038/sj.npp.1301660. PMID   18172432. S2CID   10273560.
  13. ↑ Ceide SC, Trembleau L, Haberhauer G, Somogyi L, Lu X, Bartfai T, Rebek J (November 2004). "Synthesis of galmic: a nonpeptide galanin receptor agonist". Proceedings of the National Academy of Sciences of the United States of America. 101 (48): 16727–32. Bibcode:2004PNAS..10116727C. doi: 10.1073/pnas.0407543101 . PMC   534730 . PMID   15557002.
  14. ↑ Rajarao SJ, Platt B, Sukoff SJ, Lin Q, Bender CN, Nieuwenhuijsen BW, Ring RH, Schechter LE, Rosenzweig-Lipson S, Beyer CE (October 2007). "Anxiolytic-like activity of the non-selective galanin receptor agonist, galnon". Neuropeptides. 41 (5): 307–20. doi:10.1016/j.npep.2007.05.001. PMID   17637475. S2CID   25988178.
  15. ↑ Bulaj G, Green BR, Lee HK, Robertson CR, White K, Zhang L, Sochanska M, Flynn SP, Scholl EA, Pruess TH, Smith MD, White HS (December 2008). "Design, synthesis, and characterization of high-affinity, systemically-active galanin analogues with potent anticonvulsant activities". Journal of Medicinal Chemistry. 51 (24): 8038–47. doi:10.1021/jm801088x. PMID   19053761.
  16. ↑ White HS, Scholl EA, Klein BD, Flynn SP, Pruess TH, Green BR, Zhang L, Bulaj G (April 2009). "Developing novel antiepileptic drugs: characterization of NAX 5055, a systemically-active galanin analog, in epilepsy models". Neurotherapeutics. 6 (2): 372–80. doi:10.1016/j.nurt.2009.01.001. PMC   4402707 . PMID   19332332.
  17. ↑ Robertson CR, et al. (May 2012). "Generating orally active galanin analogues with analgesic activities". ChemMedChem. 7 (5): 903–9. doi:10.1002/cmdc.201100574. PMC   4332549 . PMID   22374865.
  18. 1 2 Sollenberg UE, Runesson J, Sillard R, Langel U (March 2010). "Binding of Chimeric Peptides M617 and M871 to Galanin Receptor Type 3 Reveals Characteristics of Galanin Receptor–Ligand Interaction". International Journal of Peptide Research and Therapeutics. 16 (1): 17–22. doi:10.1007/s10989-009-9197-9. S2CID   36850989.
  19. ↑ Runesson J, Saar I, Sillard R, Langel U (2010). "M1154 – A Novel Galanin Ligand to Delineate the Galaninergic System". Proceedings of the 31st European Peptide Symposium: 452–453.
  20. ↑ Runesson J, Saar I, Lundström L, Järv J, Langel U (2009). "A novel GalR2-specific peptide agonist". Neuropeptides. 43 (3): 187–92. doi:10.1016/j.npep.2009.04.004. PMID   19467704. S2CID   36222036.
  21. ↑ Saar I, Runesson J, McNamara I, Järv J, Robinson JK, Langel U (2011). "Novel galanin receptor subtype specific ligands in feeding regulation". Neurochemistry International. 58 (6): 714–720. doi:10.1016/j.neuint.2011.02.012. PMID   21333705. S2CID   23682808.
  22. ↑ Mittapalli GK, et al. (2014). "Structure Activity Relationships of Novel Antiepileptic Drugs". Curr Med Chem. 21 (6): 722–54. doi:10.2174/0929867320666131119153215. PMID   24251563.
  23. ↑ Ogren SO, Kuteeva E, Hökfelt T, Kehr J (2006). "Galanin receptor antagonists : a potential novel pharmacological treatment for mood disorders". CNS Drugs. 20 (8): 633–54. doi:10.2165/00023210-200620080-00003. PMID   16863269. S2CID   13601784.
  24. ↑ Swanson CJ, Blackburn TP, Zhang X, Zheng K, Xu ZQ, Hökfelt T, Wolinsky TD, Konkel MJ, Chen H, Zhong H, Walker MW, Craig DA, Gerald CP, Branchek TA (November 2005). "Anxiolytic- and antidepressant-like profiles of the galanin-3 receptor (Gal3) antagonists SNAP 37889 and SNAP 398299". Proceedings of the National Academy of Sciences of the United States of America. 102 (48): 17489–94. Bibcode:2005PNAS..10217489S. doi: 10.1073/pnas.0508970102 . PMC   1283534 . PMID   16287967.
  25. ↑ Khan, SA, Zia, K, Ashraf, S, khan, A, Ul-Haq, Z (October 2021). "Theoretical investigation of selective ligand binding mode of galanin receptors". Journal of Biomolecular Structure and Dynamics. 40 (23): 12964–12974. doi:10.1080/07391102.2021.1977703. PMID   34632940. S2CID   238580114.
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