Galanin receptor pathway (WP4970)

Homo sapiens

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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 [https://pubmed.ncbi.nlm.nih.gov/33136286/ Gopalakrishnan et al.]

Authors

Dr. T. S. Keshava Prasad , Kristina Hanspers , and Martina Summer-Kutmon

Activity

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Organisms

Homo sapiens

Communities

Annotations

Disease Ontology

nervous system disease

Pathway Ontology

signaling pathway

Participants
Query Drugst.One

Label Type Compact URI Comment
SLC2A4 Protein ncbigene:6517 [Pubmed:27127795] have shown that M617 stimulates GalR1 and induces upregulation of SLC2A4 in total cell membrane and plasma membrane fractions of Male Wistar Rats adipocytes.
[Pubmed:27410235] have shown that M617 stimulates GALR1 and induces upregulation of SLC2A4 in plasma membrane of myocytes in diabetic rats.
[Pubmed: 27041232] have shown that M617 stimulates GALR1 and induces upregulation of SLC2A4 in plasma membranes of skeletal muscles in diabetic rats.
CRP Protein ncbigene:1401 [Pubmed:27127795] have shown that M617 stimulates GalR1 and induces downregulation of plasma CRP in Male Wistar Rats adipocytes.
Type your comment here
FOS Protein ncbigene:2353 [Pubmed:19272414]have shown that GAL stimulates GALR1 and induces the activation of FOS in Locus coeruleus of C57BL6/J mice brain.
[Pubmed:25405608] have shown that GAL stimulates GalR1 and  induces the upregulation of FOS in dorsomedial nucleus of the hypothalamus of Male Wistar-Han rat.
INS Protein ncbigene:3630 [Pubmed:27041232] have shown that M617 stimulates GALR1 and induces downregulation of INS in diabetic rats.
[Pubmed:27410235] have shown that M617 stimulates GALR1 and induces downregulation of INS in blood of diabetic rats.
[Pubmed:25690510] have shown that NAX-5055 stimulates GALR1 and induces downregulation of INS in CF-1 mice.
[Pubmed:25449850] have shown that M617 stimulates GALR1 and induces downregulation of INS in cardiac muscle of diabetic and normal Male Wistar rats.
YAP1 Protein ncbigene:10413 [Pubmed:28196718] have shown that GAL or M617 stimulates GALR1 and induces upregulation of YAP1 in Male Sprague-Dawley rats
CDKN1C Protein ncbigene:1028 [Pubmed: 19276245] have shown that GAL stimulates GALR2 and induces upregulation of CDKN1C in serum starved UM-SCC-1-GALR2 cells with mutant p53.
POMC Protein ncbigene:5443 [Pubmed:19272414]have shown that GAL stimulates GALR1 and induces downregulation of POMC in C57BL6/J mice.
SLC2A4 Protein ncbigene:6517 [Pubmed: 27041232] have shown that M617 stimulates GALR1 and induces the transport of SLC2A4 from cytoplasm to plasma membrane in skeletal muscle of diabetic rat
IL6 Protein ncbigene:3569 [Pubmed:24568968] have shown that GAL stimulates GALR2 and induces the upregulation of IL6 in UM-SCC-1 and UM-SCC-81B SSCHN cell lines.
ADIPOQ Protein ncbigene:9370 [Pubmed:27127795] have shown that M617 stimulates GALR1 and induces upregulation of ADIPOQ in Male Wistar Rat adipocytes.
Type your comment here
BCL2L11 Protein ncbigene:10018 [Pubmed:24168112] have shown that GAL stimulates GALR2 and induces upregulation of BCL211 in HEp-2 cell line.
VEGFA Protein ncbigene:7422 [Pubmed:24568968] have shown that GAL stimulates GALR2 and induces the upregulation of VEGFA in UM-SCC-1 and UM-SCC-81B SSCHN cell lines.
VAMP2 Protein ncbigene:6844 [Pubmed:27410235] have shown that M617 stimulates GALR1 and induces upregulation of VAMP2 in diabetic rats.
CDKN1A Protein ncbigene:1026 [Pubmed:18272487] have shown that GAL stimulates GALR2 and induces downregulation of CDKN1A in PC12-GALR2 transfected cells.
PPARG Protein ncbigene:5468 [Pubmed: 27410235] have shown that M617 stimulates GALR1 and induces upregulation of PPARG in diabetic rats.
CDKN1B Protein ncbigene:1027 [Pubmed: 19276245] have shown that GAL stimulates GALR2 and induces upregulation of CDNK1B in serum starved UM-SCC-1-GALR2 cells with mutant p53 gene.
CDKN1C Protein ncbigene:1028 [Pubmed: 19276245] have shown that GAL stimulates GALR2 and induces upregulation of CDKN1C in serum starved UM-SCC-1-GALR2 cells with mutant p53.
CREB1 Protein ncbigene:1385
SLC2A4 Protein ncbigene:6517 [Pubmed:27127795] have shown that M617 stimulates GalR1 and induces upregulation of SLC2A4 in total cell membrane and plasma membrane fractions of Male Wistar Rats adipocytes.
[Pubmed:27410235] have shown that M617 stimulates GALR1 and induces upregulation of SLC2A4 in plasma membrane of myocytes in diabetic rats.
[Pubmed: 27041232] have shown that M617 stimulates GALR1 and induces upregulation of SLC2A4 in plasma membranes of skeletal muscles in diabetic rats.
CDKN1B Protein ncbigene:1027 [Pubmed: 19276245] have shown that GAL stimulates GALR2 and induces upregulation of CDNK1B in serum starved UM-SCC-1-GALR2 cells with mutant p53 gene.

References

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  3. 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. Wittau N, Grosse R, Kalkbrenner F, Gohla A, Schultz G, Gudermann T. Oncogene. 2000 Aug 31;19(37):4199–209. PubMed Europe PMC Scholia
  4. Visualization of a functionally enhanced GFP-tagged galanin R2 receptor in PC12 cells: constitutive and ligand-induced internalization. Xia S, Kjaer S, Zheng K, Hu PS, Bai L, Jia JY, et al. Proc Natl Acad Sci U S A. 2004 Oct 19;101(42):15207–12. PubMed Europe PMC Scholia
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  8. 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. Andreis PG, Malendowicz LK, Rebuffat P, Spinazzi R, Ziolkowska A, Nussdorfer GG. Int J Mol Med. 2007 Jan;19(1):149–55. PubMed Europe PMC Scholia
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  14. Functional importance of inositol-1,4,5-triphosphate-induced intracellular Ca2+ mobilization in galanin-induced microglial migration. Ifuku M, Okuno Y, Yamakawa Y, Izumi K, Seifert S, Kettenmann H, et al. J Neurochem. 2011 Apr;117(1):61–70. PubMed Europe PMC Scholia
  15. Rap1 mediates galanin receptor 2-induced proliferation and survival in squamous cell carcinoma. Banerjee R, Henson BS, Russo N, Tsodikov A, D’Silva NJ. Cell Signal. 2011 Jul;23(7):1110–8. PubMed Europe PMC Scholia
  16. Go2 G protein mediates galanin inhibitory effects on insulin release from pancreatic β cells. Tang G, Wang Y, Park S, Bajpayee NS, Vi D, Nagaoka Y, et al. Proc Natl Acad Sci U S A. 2012 Feb 14;109(7):2636–41. PubMed Europe PMC Scholia
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  20. Activation of galanin receptor 2 stimulates large conductance Ca(2+)-dependent K(+) (BK) channels through the IP3 pathway in human embryonic kidney (HEK293) cells. Pan NC, Bai YF, Yang Y, Hökfelt T, Xu ZQD. Biochem Biophys Res Commun. 2014 Mar 28;446(1):316–21. PubMed Europe PMC Scholia
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  22. Preferential activation by galanin 1-15 fragment of the GalR1 protomer of a GalR1-GalR2 heteroreceptor complex. Borroto-Escuela DO, Narvaez M, Di Palma M, Calvo F, Rodriguez D, Millon C, et al. Biochem Biophys Res Commun. 2014 Sep 26;452(3):347–53. PubMed Europe PMC Scholia
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  24. Central injection of GalR1 agonist M617 facilitates GLUT4 expression in cardiac muscle of type 2 diabetic rats. Fang P, Shi M, Zhu Y, Zhang Z, Bo P. Exp Gerontol. 2015 May;65:85–9. PubMed Europe PMC Scholia
  25. Regulation of glucose and insulin release following acute and repeated treatment with the synthetic galanin analog NAX-5055. Flynn SP, White HS. Neuropeptides. 2015 Apr;50:35–42. PubMed Europe PMC Scholia
  26. Central injection of GALR1 agonist M617 attenuates diabetic rat skeletal muscle insulin resistance through the Akt/AS160/GLUT4 pathway. Fang P, Yu M, He B, Guo L, Huang X, Kong G, et al. Mech Ageing Dev. 2017 Mar;162:122–8. PubMed Europe PMC Scholia
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