Galanin receptor pathway (WP4970)

Galanin, a 29-30 amino acid neuropeptide named to be so, as a glycine residue occupies the position at N-terminal and an alanine residue at C-terminal. Galanin is expressed in the central and peripheral nervous systems in mammalian species. The galanin family of peptides includes ‘GMAP’ (Gaalanin- Message associated peptide), ‘GALP’ (Galanin-like Peptide), and its splice variant ‘Alarin’ along with Galanin. There are three known G-protein coupled receptor subtypes of Galanin, namely, GALR1, GALR2, and GALR3. Galaninergic signaling is predominantly inhibitory which mainly involves MAPK, AKT, AC pathways Galanin peptides have a wide range of non-neuronal functions as well as classic neuromodulatory roles, therefore it is recommended to consider as regulatory peptides. Galanin in general is associated with several biological functions such as arousal and sleep regulation, nociception, learning, inflammation, feeding, and neuroendocrine regulation. It is also implicated in diseases like Alzheimer’s, depression, epilepsy, mood disorders, stress, anxiety, diabetes mellitus, and chronic pain. The creation of this pathway is described in [ Gopalakrishnan et al.]
last edited


Keshav, Khanspers, and Mkutmon

Cited In


Homo sapiens



Disease Ontology: nervous system disease

Pathway Ontology: signaling pathway


Label Type Compact Identifier
KRT19 Rna ncbigene:3880
SLC2A4 Protein ncbigene:6517
CRP Protein ncbigene:1401
FOS Protein ncbigene:2353
INS Protein ncbigene:3630
UCP1 Rna ncbigene:7350
YAP1 Protein ncbigene:10413
CDKN1C Protein ncbigene:1028
PRKCD Rna ncbigene:5580
PPARG Rna ncbigene:5468
Go alpha 2 Unknown None
POMC Protein ncbigene:5443
SLC2A4 Protein ncbigene:6517
IL6 Protein ncbigene:3569
ADIPOQ Protein ncbigene:9370
PPARGC1A Rna ncbigene:10891
BCL2L11 Protein ncbigene:10018
Increase in plasmacorticosteronelevels Metabolite None
VEGFA Protein ncbigene:7422
VAMP2 Protein ncbigene:6844
Increase in cAMP production Metabolite None
CDKN1A Protein ncbigene:1026
Increase in bloodglucose level Metabolite None
PPARG Protein ncbigene:5468
Secretion of chlorine Metabolite None
TFAP2A Rna ncbigene:7020
CDKN1B Protein ncbigene:1027
CDKN1C Protein ncbigene:1028
Increase in plasmacorticosteronelevels Metabolite None
Increase in cAMP production Metabolite None
Increase in plasmacorticosteronelevels Metabolite None
CREB1 Protein ncbigene:1385
SLC2A4 Protein ncbigene:6517
PPARG Rna ncbigene:5468
CDKN1B Protein ncbigene:1027


  1. Li L. San-jie cream in the treatment and prevention of muscular lumps through intramuscular injections. Zhonghua Hu Li Za Zhi. 1991 Oct;26(10):434–5. PubMed Europe PMC Scholia
  2. Benya RV, Matkowskyj KA, Danilkovich A, Hecht G. Galanin causes Cl- secretion in the human colon. Potential significance of inflammation-associated NF-kappa B activation on galanin-1 receptor expression and function. Ann N Y Acad Sci. 1998 Dec 21;863:64–77. PubMed Europe PMC Scholia
  3. Wittau N, Grosse R, Kalkbrenner F, Gohla A, Schultz G, Gudermann T. The galanin receptor type 2 initiates multiple signaling pathways in small cell lung cancer cells by coupling to G(q), G(i) and G(12) proteins. Oncogene. 2000 Aug 31;19(37):4199–209. PubMed Europe PMC Scholia
  4. Xia S, Kjaer S, Zheng K, Hu P-S, Bai L, Jia J-Y, et al. Visualization of a functionally enhanced GFP-tagged galanin R2 receptor in PC12 cells: constitutive and ligand-induced internalization. Proc Natl Acad Sci U S A. 2004 Oct 19;101(42):15207–12. PubMed Europe PMC Scholia
  5. Xia S, Kjaer S, Zheng K, Hu P-S, Xu T, Hökfelt T, et al. Constitutive and ligand-induced internalization of EGFP-tagged galanin R2 and Rl receptors in PC12 cells. Neuropeptides. 2005 Jun;39(3):173–8. PubMed Europe PMC Scholia
  6. Hawes JJ, Narasimhaiah R, Picciotto MR. Galanin and galanin-like peptide modulate neurite outgrowth via protein kinase C-mediated activation of extracellular signal-related kinase. Eur J Neurosci. 2006 Jun;23(11):2937–46. PubMed Europe PMC Scholia
  7. Hobson S-A, Holmes FE, Kerr NCH, Pope RJP, Wynick D. Mice deficient for galanin receptor 2 have decreased neurite outgrowth from adult sensory neurons and impaired pain-like behaviour. J Neurochem. 2006 Nov;99(3):1000–10. PubMed Europe PMC Scholia
  8. Andreis PG, Malendowicz LK, Rebuffat P, Spinazzi R, Ziolkowska A, Nussdorfer GG. Galanin enhances corticosterone secretion from dispersed rat adrenocortical cells through the activation of GAL-R1 and GAL-R2 receptors coupled to the adenylate cyclase-dependent signaling cascade. Int J Mol Med. 2007 Jan;19(1):149–55. PubMed Europe PMC Scholia
  9. Kanazawa T, Iwashita T, Kommareddi P, Nair T, Misawa K, Misawa Y, et al. Galanin and galanin receptor type 1 suppress proliferation in squamous carcinoma cells: activation of the extracellular signal regulated kinase pathway and induction of cyclin-dependent kinase inhibitors. Oncogene. 2007 Aug 23;26(39):5762–71. PubMed Europe PMC Scholia
  10. Tofighi R, Joseph B, Xia S, Xu Z-QD, Hamberger B, Hökfelt T, et al. Galanin decreases proliferation of PC12 cells and induces apoptosis via its subtype 2 receptor (GalR2). Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2717–22. PubMed Europe PMC Scholia
  11. Mitsukawa K, Lu X, Bartfai T. Bidirectional regulation of stress responses by galanin in mice: involvement of galanin receptor subtype 1. Neuroscience. 2009 Jun 2;160(4):837–46. PubMed Europe PMC Scholia
  12. Kanazawa T, Kommareddi PK, Iwashita T, Kumar B, Misawa K, Misawa Y, et al. Galanin receptor subtype 2 suppresses cell proliferation and induces apoptosis in p53 mutant head and neck cancer cells. Clin Cancer Res. 2009 Apr 1;15(7):2222–30. PubMed Europe PMC Scholia
  13. Kim A, Park T. Diet-induced obesity regulates the galanin-mediated signaling cascade in the adipose tissue of mice. Mol Nutr Food Res. 2010 Sep;54(9):1361–70. PubMed Europe PMC Scholia
  14. Ifuku M, Okuno Y, Yamakawa Y, Izumi K, Seifert S, Kettenmann H, et al. Functional importance of inositol-1,4,5-triphosphate-induced intracellular Ca2+ mobilization in galanin-induced microglial migration. J Neurochem. 2011 Apr;117(1):61–70. PubMed Europe PMC Scholia
  15. Banerjee R, Henson BS, Russo N, Tsodikov A, D’Silva NJ. Rap1 mediates galanin receptor 2-induced proliferation and survival in squamous cell carcinoma. Cell Signal. 2011 Jul;23(7):1110–8. PubMed Europe PMC Scholia
  16. Tang G, Wang Y, Park S, Bajpayee NS, Vi D, Nagaoka Y, et al. Go2 G protein mediates galanin inhibitory effects on insulin release from pancreatic β cells. Proc Natl Acad Sci U S A. 2012 Feb 14;109(7):2636–41. PubMed Europe PMC Scholia
  17. Keimpema E, Zheng K, Barde SS, Berghuis P, Dobszay MB, Schnell R, et al. GABAergic terminals are a source of galanin to modulate cholinergic neuron development in the neonatal forebrain. Cereb Cortex. 2014 Dec;24(12):3277–88. PubMed Europe PMC Scholia
  18. Uehara T, Kanazawa T, Mizukami H, Uchibori R, Tsukahara T, Urabe M, et al. Novel anti-tumor mechanism of galanin receptor type 2 in head and neck squamous cell carcinoma cells. Cancer Sci. 2014 Jan;105(1):72–80. PubMed Europe PMC Scholia
  19. Banerjee R, Van Tubergen EA, Scanlon CS, Vander Broek R, Lints JP, Liu M, et al. The G protein-coupled receptor GALR2 promotes angiogenesis in head and neck cancer. Mol Cancer Ther. 2014 May;13(5):1323–33. PubMed Europe PMC Scholia
  20. Pan NC, Bai Y-F, Yang Y, Hökfelt T, Xu Z-QD. Activation of galanin receptor 2 stimulates large conductance Ca(2+)-dependent K(+) (BK) channels through the IP3 pathway in human embryonic kidney (HEK293) cells. Biochem Biophys Res Commun. 2014 Mar 28;446(1):316–21. PubMed Europe PMC Scholia
  21. Kanazawa T, Misawa K, Misawa Y, Maruta M, Uehara T, Kawada K, et al. Galanin receptor 2 utilizes distinct signaling pathways to suppress cell proliferation and induce apoptosis in HNSCC. Mol Med Rep. 2014 Sep;10(3):1289–94. PubMed Europe PMC Scholia
  22. Borroto-Escuela DO, Narvaez M, Di Palma M, Calvo F, Rodriguez D, Millon C, et al. Preferential activation by galanin 1-15 fragment of the GalR1 protomer of a GalR1-GalR2 heteroreceptor complex. Biochem Biophys Res Commun. 2014 Sep 26;452(3):347–53. PubMed Europe PMC Scholia
  23. Amorim D, David-Pereira A, Marques P, Puga S, Rebelo P, Costa P, et al. A role of supraspinal galanin in behavioural hyperalgesia in the rat. PLoS One. 2014 Nov 18;9(11):e113077. PubMed Europe PMC Scholia
  24. Fang P, Shi M, Zhu Y, Zhang Z, Bo P. Central injection of GalR1 agonist M617 facilitates GLUT4 expression in cardiac muscle of type 2 diabetic rats. Exp Gerontol. 2015 May;65:85–9. PubMed Europe PMC Scholia
  25. Flynn SP, White HS. Regulation of glucose and insulin release following acute and repeated treatment with the synthetic galanin analog NAX-5055. Neuropeptides. 2015 Apr;50:35–42. PubMed Europe PMC Scholia
  26. Fang P, Yu M, He B, Guo L, Huang X, Kong G, et al. Central injection of GALR1 agonist M617 attenuates diabetic rat skeletal muscle insulin resistance through the Akt/AS160/GLUT4 pathway. Mech Ageing Dev. 2017 Mar;162:122–8. PubMed Europe PMC Scholia
  27. Zhang Z, Fang P, He B, Guo L, Runesson J, Langel Ü, et al. Central Administration of Galanin Receptor 1 Agonist Boosted Insulin Sensitivity in Adipose Cells of Diabetic Rats. J Diabetes Res. 2016;2016:9095648. PubMed Europe PMC Scholia
  28. Bu L, Chang X, Cheng X, Yao Q, Su B, Sheng C, et al. Activated central galanin type 1 receptor alleviated insulin resistance in diabetic rat muscle. J Neurosci Res. 2016 Oct;94(10):947–55. PubMed Europe PMC Scholia
  29. Webling K, Runesson J, Lang A, Saar I, Kofler B, Langel Ü. Ala5-galanin (2-11) is a GAL2R specific galanin analogue. Neuropeptides. 2016 Dec;60:75–82. PubMed Europe PMC Scholia
  30. McMillin M, Frampton G, Grant S, DeMorrow S. The Neuropeptide Galanin Is Up-Regulated during Cholestasis and Contributes to Cholangiocyte Proliferation. Am J Pathol. 2017 Apr;187(4):819–30. PubMed Europe PMC Scholia
  31. Li Y, Mei Z, Liu S, Wang T, Li H, Li X-X, et al. Galanin Protects from Caspase-8/12-initiated Neuronal Apoptosis in the Ischemic Mouse Brain via GalR1. Aging Dis. 2017 Feb 1;8(1):85–100. PubMed Europe PMC Scholia
  32. Fang P, Zhang L, Yu M, Sheng Z, Shi M, Zhu Y, et al. Activiated galanin receptor 2 attenuates insulin resistance in skeletal muscle of obese mice. Peptides. 2018 Jan;99:92–8. PubMed Europe PMC Scholia
  33. Gopalakrishnan L, Chatterjee O, Raj C, Pullimamidi D, Advani J, Mahadevan A, et al. An assembly of galanin-galanin receptor signaling network. J Cell Commun Signal. 2021 Jun;15(2):269–75. PubMed Europe PMC Scholia