Galanin receptor

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galanin receptor 1
Identifiers
Symbol GALR1
Alt. symbols GALNR1, GALNR
Entrez 2587
HUGO 4132
OMIM 600377
RefSeq NM_001480
UniProt P47211
Other data
Locus Chr. 18 q23
galanin receptor 2
Identifiers
Symbol GALR2
Entrez 8811
HUGO 4133
OMIM 603691
RefSeq NM_003857
UniProt O43603
Other data
Locus Chr. 17 q25.3
galanin receptor 3
Identifiers
Symbol GALR3
Entrez 8484
HUGO 4134
OMIM 603692
RefSeq NM_003614
UniProt O60755
Other data
Locus Chr. 22 q12.2-13.1

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

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[edit]

Agonists[edit]

Non-selective
GAL1 selective


GAL1/2 selective
  • M1154 - has no GalR3 interaction[19]
GAL2 selective
  • Galanin 2-11 amide - also called AR-M 1896, anticonvulsant in mice, CAS# 367518-31-8
  • M1145 - seletive compared to both GalR1 and GalR3 [20]
  • M1153 - seletive compared to both GalR1 and GalR3[21]
  • CYM 2503 (positive allosteric modulator)[22]

Antagonists[edit]

Non-selective
  • M35 peptide
GAL1 selective
  • SCH-202,596
GAL2 selective
GAL3 selective

References[edit]

  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. 
  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 : CMLS 65 (12): 1864–71. doi:10.1007/s00018-008-8161-8. PMID 18500639. 
  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. 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. 
  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 : CMLS 65 (12): 1854–63. doi:10.1007/s00018-008-8160-9. PMID 18500640. 
  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. 
  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. 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. 
  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 : the Journal of the American Society for Experimental NeuroTherapeutics 6 (2): 372–80. doi:10.1016/j.nurt.2009.01.001. PMID 19332332. 
  17. ^ Robertson, CR; et al. (May 2012). "Generating orally active galanin analogues with analgesic activities.". ChemMedChem. (2012) 7 (5): 903–9. doi:10.1002/cmdc.201100574. PMID 22374865. 
  18. ^ a b 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 therapeutids 16 (1): 17–22. doi:10.1007/s10989-009-9197-9. 
  19. ^ Runesson J, Saar I, Sillard R, Langel U (2010). "M1154 – A Novel Galanin Ligand to Delineate the Galaninergic System". Proceeding 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. 
  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. 
  22. ^ Mittapalli, GK; et al. (2014). "Structure Activity Relationships of Novel Antiepileptic Drugs.". Curr Med Chem. (2013) 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. 
  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. doi:10.1073/pnas.0508970102. PMC 1283534. PMID 16287967. 

External links[edit]