Alternative titles; symbols
HGNC Approved Gene Symbol: GALR1
Cytogenetic location: 18q23 Genomic coordinates (GRCh38): 18:77,249,848-77,277,900 (from NCBI)
Galanin (137035) is an important neuromodulator present in the brain, gastrointestinal system, and hypothalamopituitary axis. It is a 30-amino acid non-C-terminally amidated peptide that potently stimulates growth hormone secretion, inhibits cardiac vagal slowing of heart rate, abolishes sinus arrhythmia, and inhibits postprandial gastrointestinal motility. The actions of galanin are mediated through interaction with specific membrane receptors that are members of the 7-transmembrane family of G protein-coupled receptors. Walli et al. (1994) identified and biochemically characterized a specific receptor for galanin in various areas of human brain. Habert-Ortoli et al. (1994) also cloned a functional human galanin receptor.
Parker et al. (1995) cloned a rat galanin receptor cDNA from an insulinoma cell line. This predicted a 346-amino acid G protein-coupled receptor with 92% homology to the human galanin receptor. Hydrophobicity analysis predicted 7 transmembrane domains in the protein.
Lorimer and Benya (1996) quantified GALR1 expression in the gastrointestinal tract.
Hecht et al. (1999) showed that pathogenic E. coli, but not normal commensal organisms, increase GALR1, which they called GAL1R, mRNA synthesis and (125)I-galanin binding sites. In mice infected with enterohemorrhagic E. coli by gavage, infection caused a progressive increase in both nuclear factor kappa-B (see 164011) activation and GALR1 expression, with maximal levels of both observed 3 days after gavage. With Ussing chamber studies, they showed that colons infected with enterohemorrhagic E. coli, but not those exposed to normal colonic flora, markedly increased short-circuit current in response to galanin. These data indicated that pathogen-induced increases in GALR1 expression by epithelial cells lining the colon represent a novel unifying pathway responsible for at least a portion of the excessive fluid secretion observed during infectious diarrhea.
Jacoby et al. (1997) demonstrated that the GALNR gene spans approximately 15 to 20 kb in both human and mouse and that its structural organization is conserved and unique among G protein-coupled receptors. The coding sequence is contained in 3 exons, with exon 1 encoding the N-terminal portion of the receptor and the first 5 transmembrane domains. Exon 2 encodes the third intracellular loop, while exon 3 encodes the remainder of the receptor, from transmembrane domain 6 to the C terminus of the receptor protein. The mouse and human GALR1 receptor proteins are 348 and 349 amino acids long, respectively, and display 93% identity at the amino acid level.
Nicholl et al. (1995) mapped the GALR1 gene to 18q23 by fluorescence in situ hybridization. Cody et al. (1997) demonstrated that GALNR1 and the myelin basic protein gene (159430) are closely linked, as indicated by their colocation on YAC clones. Simoneaux et al. (1997) mapped the Galnr1 gene to mouse chromosome 18. Jacoby et al. (1997) localized the mouse Galnr gene to 18E4, a region consistent with the previously reported localization of human GALNR to 18q23.
Cody, J. D., Hale, D. E., Brkanac, Z., Kaye, C. I., Leach, R. J. Growth hormone insufficiency associated with haploinsufficiency at 18q23. Am. J. Med. Genet. 71: 420-425, 1997. [PubMed: 9286448]
Habert-Ortoli, E., Amiranoff, B., Loquet, I., Laburthe, M., Mayaux, J.-F. Molecular cloning of a functional human galanin receptor. Proc. Nat. Acad. Sci. 91: 9780-9783, 1994. [PubMed: 7524088] [Full Text: https://doi.org/10.1073/pnas.91.21.9780]
Hecht, G., Marrero, J. A., Danilkovich, A., Matkowskyj, K. A., Savkovic, S. D., Koutsouris, A., Benya, R. V. Pathogenic Escherichia coli increase Cl- secretion from intestinal epithelia by upregulating galanin-1 receptor expression. J. Clin. Invest. 104: 253-262, 1999. [PubMed: 10430606] [Full Text: https://doi.org/10.1172/JCI6373]
Jacoby, A. S., Webb, G. C., Liu, M. L., Kofler, B., Hort, Y. J., Fathi, Z., Bottema, C. D. K., Shine, J., Iismaa, T. P. Structural organization of the mouse and human GALR1 galanin receptor genes (Galnr and GALNR) and chromosomal localization of the mouse gene. Genomics 45: 496-508, 1997. [PubMed: 9367674] [Full Text: https://doi.org/10.1006/geno.1997.4960]
Lorimer, D. D., Benya, R. V. Cloning and quantification of galanin-1 receptor expression by mucosal cells lining the human gastrointestinal tract. Biochem. Biophys. Res. Commun. 222: 379-385, 1996. [PubMed: 8670213] [Full Text: https://doi.org/10.1006/bbrc.1996.0752]
Nicholl, J., Kofler, B., Sutherland, G. R., Shine, J., Iismaa, T. P. Assignment of the gene encoding human galanin receptor (GALNR) to 18q23 by in situ hybridization. Genomics 30: 629-630, 1995. [PubMed: 8825658] [Full Text: https://doi.org/10.1006/geno.1995.1292]
Parker, E. M., Izzarelli, D. G., Nowak, H. P., Mahle, C. D., Iben, L. G., Wang, J., Goldstein, M. E. Cloning and characterization of the rat GALR1 galanin receptor from Rin14B insulinoma cells. Molec. Brain Res. 34: 179-189, 1995. [PubMed: 8750821] [Full Text: https://doi.org/10.1016/0169-328x(95)00159-p]
Simoneaux, D. K., Leach, R. J., O'Connell, P. Galanin receptor 1 gene (Galnr1) is tightly linked to the myelin basic protein gene on chromosome 18 in mouse. Mammalian Genome 8: 875 only, 1997. [PubMed: 9337411] [Full Text: https://doi.org/10.1007/s003359900630]
Walli, R., Schafer, H., Morys-Wortmann, C., Paetzold, G., Nustede, R., Schmidt, W. E. Identification and biochemical characterization of the human brain galanin receptor. J. Molec. Endocr. 13: 347-356, 1994. [PubMed: 7534460] [Full Text: https://doi.org/10.1677/jme.0.0130347]