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Gene Review

GAL  -  galanin/GMAP prepropeptide

Homo sapiens

Synonyms: GAL-GMAP, GAL1, GALN, GLNN, GMAP, ...
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Disease relevance of GAL


Psychiatry related information on GAL


High impact information on GAL

  • Apart from its role in the onset of drive to eat, the circadian patterns of gene expression of NPY, GAL, and POMC denote independent control of the timing device on the synthesis and availability for release of orexigenic signals [10].
  • Within this formulation, the coexisting orexigenic signals (NPY, NE, GAL, GABA, and AgrP) represent either another level of redundancy or it is possible that these signals operate within the ARN as reinforcing agents to varying degrees under different circumstances [10].
  • Induction of GAL1 increases H3 acetylation per nucleosome in the ORF, dependent on SAGA integrity but not the alternative Gcn5p-HAT complex ADA [11].
  • A recent study has shown that mice containing a loss-of-function mutation in the gene encoding galanin exhibit decreased peripheral nerve regeneration after a lesion [12].
  • Co-existence of galanin and acetylcholine: is galanin involved in memory processes and dementia [13]?

Chemical compound and disease context of GAL


Biological context of GAL

  • We screened the coding region of GAL (including 444 bp of its promoter region) and GALR1 for mutations using single-strand conformation polymorphism analysis and denaturing HPLC in up to 191 obese children and adolescents and 106 healthy underweight young adults (students) [2].
  • Galanin-like immunoreactivity (GAL-LI) and specific GAL binding sites have been shown to be widely distributed in the central nervous system (CNS) and in CNS tumors [4].
  • No correlation could be found between GAL-LI, the level of GAL binding and proliferative activity as determined by immunostaining with the cell proliferation marker Ki-67 [4].
  • SAL inhibited the GH response to GHRH (AUC: 282.6 +/- 102.7 vs 1083.6 +/- 176.5 micrograms/l/h, p < 0.05) and, although not significantly, that to GAL (263.9 +/- 103.7 vs 418.4 +/- 70.4 micrograms/l/h) [17].
  • We combined the mutagenesis results with data on the pharmacophores (Trp2, Tyr9) of galanin and with molecular modelling of the receptor using bacteriorhodopsin as a model [18].

Anatomical context of GAL


Associations of GAL with chemical compounds

  • Thus, in the present study, we examined the influence of pre-treatment with guanine nucleotides on 125I-GAL binding in multiple regions of normal and AD brain [5].
  • In the opossum, immunoreactivity for GAL was the most intense and abundant followed by SP, which was followed by VIP [21].
  • The results also indicate that GAL is not coreleased with E or NE in response to the exercise-induced stress condition [22].
  • GAL is also endowed with an inhibiting effect on glucose-stimulated insulin release in animals, but not in man [23].
  • GAL is colocalized with corticotropin (ACTH) in the human pituitary and with epinephrine (E) and norepinephrine (NE) in chromaffin cells of the adrenal medulla [22].

Physical interactions of GAL

  • In addition, pre-treatment with guanine nucleotides may provide a more accurate measurement of GALR density since it would avoid the masking of GALRs by residual binding of endogenous GAL [5].
  • In the medial occipital gyrus, galanin binding in the AD cases was not different from controls in any cortical layer despite a reduction in choline acetyltransferase activity [24].
  • Significantly increased leptin and galanin levels in postmenopausal obese women coupled with decreased NPY levels revealed some changes in the neuropeptides regulating eating behavior, which may be the reason for the onset of postmenopausal obesity [25].
  • There are three well-characterized G-protein coupled galanin receptors subtypes (GalR1-3) [26].

Co-localisations of GAL

  • In rats, VP is colocalized with galanin (GAL) in several brain regions [27].

Regulatory relationships of GAL

  • Previous studies showed that GH-releasing hormone (GHRH) stimulates galanin release from pituitary cells in vitro [28].
  • The galanin-induced PRL release was significantly increased in patients with Cushing's disease [29].
  • These data suggest that the effects of galanin on basal and stimulated GH release are mediated via different receptor subtypes and that the human equivalent of GAL-R(W) may exist [30].
  • 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 [31].
  • Administration of CRH induced a modest but significant increase in galanin concentrations at all three sampling sites [32].

Other interactions of GAL

  • Major challenges in this field include linking the receptor clones with each of the known physiological actions of galanin and evaluating the evidence for additional galanin receptor subtypes [33].
  • Hypothalamic concentrations of galanin peptide were also increased in hGHRH transgenic mice, but were not greater than those in nontransgenic siblings until 4 months of age [28].
  • One example, 1,3-dihydro-1-phenyl-3-[[3-(trifluoromethyl)phenyl]imino]-2H-indol-2-one (9), was shown to have high affinity for the human GAL3 receptor (Ki=17 nM) and to be highly selective for GAL3 over a broad panel of targets, including GAL1 and GAL2 [34].
  • Neurons positive for GA and TH were rare [35].
  • Processing of neuropeptide Y, galanin, and somatostatin in the cerebrospinal fluid of patients with Alzheimer's disease and frontotemporal dementia [36].

Analytical, diagnostic and therapeutic context of GAL


  1. Galanin receptor 1 has anti-proliferative effects in oral squamous cell carcinoma. Henson, B.S., Neubig, R.R., Jang, I., Ogawa, T., Zhang, Z., Carey, T.E., D'Silva, N.J. J. Biol. Chem. (2005) [Pubmed]
  2. Human galanin (GAL) and galanin 1 receptor (GALR1) variations are not involved in fat intake and early onset obesity. Schäuble, N., Reichwald, K., Grassl, W., Bechstein, H., Müller, H.C., Scherag, A., Geller, F., Utting, M., Siegfried, W., Goldschmidt, H., Blundell, J., Lawton, C., Alam, R., Whybrow, S., Stubbs, J., Platzer, M., Hebebrand, J., Hinney, A. J. Nutr. (2005) [Pubmed]
  3. Effect of human galanin on the response of circulating catecholamines to hypoglycemia in man. degli Uberti, E.C., Ambrosio, M.R., Bondanelli, M., Trasforini, G., Valentini, A., Rossi, R., Margutti, A., Campo, M. Eur. J. Endocrinol. (1995) [Pubmed]
  4. Galanin and galanin receptors in human gliomas. Berger, A., Santic, R., Almer, D., Hauser-Kronberger, C., Huemer, M., Humpel, C., Stockhammer, G., Sperl, W., Kofler, B. Acta Neuropathol. (2003) [Pubmed]
  5. Increased galanin receptor occupancy in Alzheimer's disease. McMillan, P.J., Peskind, E., Raskind, M.A., Leverenz, J.B. Neurobiol. Aging (2004) [Pubmed]
  6. Role of neuropeptides in the regulation of feeding behavior: a review of cholecystokinin, bombesin, neuropeptide Y, and galanin. Lee, M.C., Schiffman, S.S., Pappas, T.N. Neuroscience and biobehavioral reviews. (1994) [Pubmed]
  7. Sleep and endocrinology. Steiger, A. J. Intern. Med. (2003) [Pubmed]
  8. Effects of galanin on growth hormone and prolactin secretion in anorexia nervosa. De Marinis, L., Mancini, A., Valle, D., Bianchi, A., Gentilella, R., Milardi, D., Mascadri, C., Giustina, A. Metab. Clin. Exp. (2000) [Pubmed]
  9. Galanin receptor antagonists : a potential novel pharmacological treatment for mood disorders. Ogren, S.O., Kuteeva, E., Hökfelt, T., Kehr, J. CNS drugs. (2006) [Pubmed]
  10. Interacting appetite-regulating pathways in the hypothalamic regulation of body weight. Kalra, S.P., Dube, M.G., Pu, S., Xu, B., Horvath, T.L., Kalra, P.S. Endocr. Rev. (1999) [Pubmed]
  11. Gcn5 promotes acetylation, eviction, and methylation of nucleosomes in transcribed coding regions. Govind, C.K., Zhang, F., Qiu, H., Hofmeyer, K., Hinnebusch, A.G. Mol. Cell (2007) [Pubmed]
  12. Can galanin also be considered as growth-associated protein 3.2? Zigmond, R.E. Trends Neurosci. (2001) [Pubmed]
  13. Co-existence of galanin and acetylcholine: is galanin involved in memory processes and dementia? Crawley, J.N., Wenk, G.L. Trends Neurosci. (1989) [Pubmed]
  14. Galanin receptor plasticity within the nucleus basalis in early and late Alzheimer's disease: an in vitro autoradiographic analysis. Mufson, E.J., Deecher, D.C., Basile, M., Izenwasse, S., Mash, D.C. Neuropharmacology (2000) [Pubmed]
  15. Galanin and its receptors in neurological disorders. Lundström, L., Elmquist, A., Bartfai, T., Langel, U. Neuromolecular Med. (2005) [Pubmed]
  16. Molecular cloning of a functional human galanin receptor. Habert-Ortoli, E., Amiranoff, B., Loquet, I., Laburthe, M., Mayaux, J.F. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  17. Interaction of salbutamol and galanin on both basal and growth hormone releasing hormone-stimulated growth hormone secretion in humans. Arvat, E., Ramunni, J., Gianotti, L., Di Vito, L., Maccario, M., Camanni, F., Ghigo, E. J. Endocrinol. Invest. (1995) [Pubmed]
  18. Delineation of the peptide binding site of the human galanin receptor. Kask, K., Berthold, M., Kahl, U., Nordvall, G., Bartfai, T. EMBO J. (1996) [Pubmed]
  19. 125I-labeled galanin binding sites in congenital innervation defects of the distal colon. Berger, A., Kofler, B., Santic, R., Zipperer, E., Sperl, W., Hauser-Kronberger, C. Acta Neuropathol. (2003) [Pubmed]
  20. Distribution and actions of galanin and vasoactive intestinal peptide in the human colon. Burleigh, D.E., Furness, J.B. Neuropeptides (1990) [Pubmed]
  21. Structure and chemical coding of human, canine and opossum gallbladder ganglia. Talmage, E.K., Pouliot, W.A., Schemann, M., Mawe, G.M. Cell Tissue Res. (1996) [Pubmed]
  22. Evaluation of circulating galanin levels after exercise-induced pituitary hormone secretion in man. Ceresini, G., Marchini, L., Fabbo, A., Freddi, M., Pasolini, G., Reali, N., Troglio, G., Valenti, G. Metab. Clin. Exp. (1997) [Pubmed]
  23. Interactions of galanin and arginine on growth hormone, prolactin, and insulin secretion in man. Ghigo, E., Maccario, M., Arvat, E., Valetto, M.R., Valente, F., Nicolosi, M., Mazza, E., Martina, V., Cocchi, D., Camanni, F. Metab. Clin. Exp. (1992) [Pubmed]
  24. Galanin receptor binding sites in the temporal and occipital cortex are minimally affected in Alzheimer's disease. Ikeda, M., Dewar, D., McCulloch, J. Neurosci. Lett. (1995) [Pubmed]
  25. Influence of obesity and menopausal status on serum leptin, cholecystokinin, galanin and neuropeptide Y levels. Milewicz, A., Bidzińska, B., Mikulski, E., Demissie, M., Tworowska, U. Gynecol. Endocrinol. (2000) [Pubmed]
  26. Galanin/GALP receptors and CNS homeostatic processes. Robinson, J.K., Bartfai, T., Langel, U. CNS & neurological disorders drug targets. (2006) [Pubmed]
  27. Galanin antagonizes vasopressin-stimulated flank marking in male golden hamsters. Ferris, C.F., Delville, Y., Bonigut, S., Miller, M.A. Brain Res. (1999) [Pubmed]
  28. Galanin gene expression is increased in the anterior pituitary gland of the human growth hormone-releasing hormone transgenic mouse. Moore, J.P., Morrison, D.G., Hyde, J.F. Endocrinology (1994) [Pubmed]
  29. Enhanced prolactin responsiveness to galanin in patients with Cushing's disease. Invitti, C., Pecori Giraldi, F., Tagliaferri, A., Scacchi, M., Dubini, A., Cavagnini, F. Clin. Endocrinol. (Oxf) (1993) [Pubmed]
  30. The differential effects of galanin-(1-30) and -(3-30) on anterior pituitary hormone secretion in vivo in humans. Todd, J.F., Edwards, C.M., Ghatei, M.A., Bloom, S.R. Am. J. Physiol. Endocrinol. Metab. (2000) [Pubmed]
  31. 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, P.G., Malendowicz, L.K., Rebuffat, P., Spinazzi, R., Ziolkowska, A., Nussdorfer, G.G. Int. J. Mol. Med. (2007) [Pubmed]
  32. Galanin is released by adrenocorticotropin-secreting pituitary adenomas in vivo and in vitro. Invitti, C., Pecori Giraldi, F., Dubini, A., Moroni, P., Losa, M., Piccoletti, R., Cavagnini, F. J. Clin. Endocrinol. Metab. (1999) [Pubmed]
  33. Galanin receptor subtypes. Branchek, T.A., Smith, K.E., Gerald, C., Walker, M.W. Trends Pharmacol. Sci. (2000) [Pubmed]
  34. 3-arylimino-2-indolones are potent and selective galanin GAL3 receptor antagonists. Konkel, M.J., Lagu, B., Boteju, L.W., Jimenez, H., Noble, S., Walker, M.W., Chandrasena, G., Blackburn, T.P., Nikam, S.S., Wright, J.L., Kornberg, B.E., Gregory, T., Pugsley, T.A., Akunne, H., Zoski, K., Wise, L.D. J. Med. Chem. (2006) [Pubmed]
  35. Galanin immunoreactive neurons in the human hypothalamus: colocalization with vasopressin-containing neurons. Gai, W.P., Geffen, L.B., Blessing, W.W. J. Comp. Neurol. (1990) [Pubmed]
  36. Processing of neuropeptide Y, galanin, and somatostatin in the cerebrospinal fluid of patients with Alzheimer's disease and frontotemporal dementia. Nilsson, C.L., Brinkmalm, A., Minthon, L., Blennow, K., Ekman, R. Peptides (2001) [Pubmed]
  37. Neuropeptides in idiopathic chronic constipation (slow transit constipation). Sjölund, K., Fasth, S., Ekman, R., Hultén, L., Jiborn, H., Nordgren, S., Sundler, F. Neurogastroenterol. Motil. (1997) [Pubmed]
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