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Gene Review

Gal  -  galanin/GMAP prepropeptide

Rattus norvegicus

Synonyms: Galanin peptides, Galn

Disease relevance of Gal


Psychiatry related information on Gal

  • Galanin (GAL) is a widely distributed neuropeptide with diverse biological effects including modulation of hormone release, antinociception and modification of feeding behavior [6].
  • Galanin immunoreactive fibers hyperinnervate remaining cholinergic basal forebrain neurons in Alzheimer's disease, perhaps exacerbating the cholinergic deficit [7].
  • Six-hour selective REM sleep deprivation increases the expression of the galanin gene in the hypothalamus of rats [8].
  • Galanin is a 29/30 amino acid neuropeptide that has been shown to impair learning and memory task performance and also have roles in somatosensation, stress responses, sexual behavior, and feeding regulation [9].
  • Gal-R1 mRNA was abundant in the SON (and magnocellular PVN) of control rats and levels were increased in these same cells after 4 days of salt-loading (2% NaCl solution as drinking water) or water deprivation [10].
  • Galanin and Gal2-11 (a GalR2/3 agonist) inhibited the neurotoxicity induced by Abeta(25-35) or Abeta(1-42) in primary cultured hippocampal neurons of rats. Additionally, galanin inhibited the activation of p53, Bax, and caspase-3 and reversed the down-regulation of Bcl-2 induced by Abeta(25-35) in cultured hippocampal neurons. In the Morris water maze, intra-CA1 injections of Abeta(25-35) caused spatial learning deficits and protein dysregulation in the hippocampus (p53, Bax, and MAP2), which were both blocked by galanin. [11]
  • In the forced swim test, an animal model of depression, intracerebroventricular (i.c.v.) infusion of galanin, M617 (GalR1 agonist), and M871 (GalR2 antagonist) increased immobility time (prodepressive effect) compared to sham rats. Conversely, AR-M1896 (GalR2/3 agonist) decreased immobility time (antidepressant effect). In addition, 5-HT(1A) mRNA levels were downregulated following i.c.v. galanin, M617 or AR-M1896 infusion [12].
  • Acute administration of the SNAP37889 (GalR3 selective antagonist) enhanced social interaction, increased punished drinking (anxiolytic effect), and decreased immobility in the forced swim test (antidepressant effect). SNAP37889 partially antagonized the galanin-evoked reduction in hippocampal serotonin and partially reversed the galanin-evoked inhibition of dorsal raphe cell firing and galanin-evoked hyperpolarizing currents [13].
  • Rats exposed to three weeks of chronic mild stress, an animal model of stress-induced anhedonia, showed decreased mRNA levels of galanin in the ventromedial and dorsomedial hypothalamic nuclei as well as the lateral hypothalamic area [14].
  • Systemic administration of yohimbine (α2-adrenergic autoreceptor antagonist) i.p. and prior immobilization stress both had an anxiogenic effect on elevated plus maze (EPM) behavior; however, systemic yohimbine pretreatment before immobilization stress (yohimbine + stress) had a paradoxical anxiolytic effect on EPM behavior. Bilateral administration of M40 (GalR antagonist) into the central nucleus of the amygdala (CeA) blocked both the anxiolytic effects of systemic yohimbine and galanin pretreatment [15]. In a second experiment 6-OHDA lesions of the noradrenergic innervation of the CeA did not alter the galanin-mediated anxiolytic effect of yohimbine + stress on EPM behavior. This suggested that the effect was derived from galanin release from local neurons in the intraamygdalar bed nucleus of the stria terminalis, which showed activation of galanin neurons after yohimbine + stress, and not from corelease of galanin from noradrenergic terminals in the CeA [16].
  • In the visible burrow system (VBS), a naturalistic, social stress paradigm, male and female rats are housed together and dominance hierarchies are formed which are chronicly stressful to the subordinate rat. After two weeks of VBS, subordinate rats showed elevated levels of preprogalanin mRNA in the locus coeruleus, which were positively correleated with wounds on days 7 and 14 and negatively correleated with body weight on day 14 [17].

High impact information on Gal


Chemical compound and disease context of Gal


Biological context of Gal

  • Low (basal) concentrations of GAL were detected in control ribs, whereas at 1 and 2 weeks postfracture, callus samples contained markedly increased levels of peptide ( approximately 32- and 18-fold increase, respectively, relative to controls; P < 0.01), revealing a strong upregulation during bone healing [1].
  • Thus, severance of skeletal-associated nerves during fracture could similarly increase local GAL concentrations and thereby influence fracture healing [1].
  • The IC50 for galanin 5-29 was 200 nM, whereas 8-29 and 1-15 were > 1 microM [26].
  • The deduced amino acid sequence of rat galanin is 90% similar to porcine galanin, with all three amino acid differences in the C-terminal heptapeptide [27].
  • We have isolated and characterized cDNAs encoding rat galanin from a cDNA library prepared from rat hypothalamic tissue [27].

Anatomical context of Gal


Associations of Gal with chemical compounds

  • Tetrodotoxin (TTX) did not suppress the galanin excitatory effect, whereas the effect of galanin 1-16 on gastric contraction was increased by TTX- or N-nitro-L-arginine, an inhibitor of nitric oxide synthase [29].
  • In the precursor, galanin includes a C-terminal glycine and is flanked on each side by dibasic tryptic cleavage sites [27].
  • These results provide the first evidence of a physiological regulator (estrogen) of the expression of the galanin gene [2].
  • Galanin (GAL) has been proposed to be an inhibitory modulator of cholinergic memory pathways because it acts within the hippocampus to inhibit the release and antagonize the postsynaptic actions of acetylcholine [30].
  • Galanin (GAL) inhibits midbrain dopamine (DA) activity in several experimental paradigms, yet the mechanism underlying this inhibition is unclear [31].

Physical interactions of Gal

  • Because a portion of GAL receptors in this region have been postulated to function as presynaptic auto-receptors on cholinergic fiber terminals, the reduction in GAL binding sites with age may be a consequence of age-related alterations in GAL receptor expression by basal forebrain cholinergic neurons which project to the ventral hippocampus [30].
  • Clustering of multiple Gal (or GalNAc) residues increased the binding affinity to M-ASGP-BP as well as to HHL [32].
  • We conclude that RHL-1 is the Ca(2+)-dependent Lf receptor on hepatocytes and that it binds Lf in a Gal-independent manner [33].
  • In view of these data and of previous results, we conclude that the galanin receptors in GH3 and in RINm5F cells couple mainly to the G(0) protein consisting of alpha 01 beta 2 gamma 2 to inhibit Ca2+ channels and use alpha 01beta 3 gamma 4 less efficiently [34].

Co-localisations of Gal

  • Neuropeptide Y-like immunoreactivity colocalized with galanin- or VIP/PHI-like immunoreactivity in some nerve fibres [35].
  • GAL is extensively colocalized within these steroid-sensitive cell groups where its expression is upregulated by gonadal hormones [36].
  • Galanin is a neuropeptide that is colocalized with GHRH in hypothalamic neurons and is thought to be involved in generating the episodic pattern of GH secretion [37].
  • Triple-immunofluorescence staining showed that galanin-like immunoreactivity co-localized with substance P- and calcitonin gene-related peptide-like immunoreactivities in many nerve fibres and terminals in laminae I and II of the dorsal horn [38].
  • Thus galanin-like immunoreactivity sometimes also co-localized with cholecystokinin- and neuropeptide tyrosine-like immunoreactivities in calcitonin gene-related peptide-immunoreactive terminals and in some large dense-core vesicles in such terminals [38].
  • Galanin immunoreactive cells and dendrites are innervated by dopaminergic fiber terminals in the laterodorsal division of the bed nucleus of the stria terminalis (BST) and by noradrenergic axons in the lateroventral BST [39].

Regulatory relationships of Gal


Other interactions of Gal

  • In the present experiments, the effects of two GAL receptor antagonists, C7 and galantide, on fat consumption and central overexpression of GAL were investigated [43].
  • A small population of NPY-containing fibers also seemed to contain galanin (cat only) [44].
  • By real-time polymerase chain reaction and in situ hybridisation, mRNA levels of neuropeptide Y, but not pro-opiomelanocortin and galanin-like peptide, were significantly increased in the ARC of GK rats at 11 weeks, but not 26 weeks [45].
  • Neurons expressing VIP mRNA were mainly small sized, with a cross-sectional area of approximately 700 microns2, while those expressing GAL mRNA were both small (approximately 700 microns2) and medium (approximately 1,300 microns2) sized [46].
  • These results suggest that 6-h selective RSD may not be sufficient to induce the activation of the hypothalamo-pituitary adrenal axis, and that the expression of the galanin gene in the hypothalamus reacts more readily against the loss of REM sleep in comparison to other hypothalamic neuropeptides such as arginine vasopressin, oxytocin and orexins [8].

Analytical, diagnostic and therapeutic context of Gal


  1. Expression of galanin and galanin receptor-1 in normal bone and during fracture repair in the rat. McDonald, A.C., Schuijers, J.A., Shen, P.J., Gundlach, A.L., Grills, B.L. Bone (2003) [Pubmed]
  2. Isolation and characterization of a complementary DNA (galanin) clone from estrogen-induced pituitary tumor messenger RNA. Vrontakis, M.E., Peden, L.M., Duckworth, M.L., Friesen, H.G. J. Biol. Chem. (1987) [Pubmed]
  3. Intracerebroventricular galanin-like peptide induces different brain activation compared with galanin. Lawrence, C.B., Williams, T., Luckman, S.M. Endocrinology (2003) [Pubmed]
  4. Galanin modulates neuronal and synaptic properties in the rat supraoptic nucleus in a use and state dependent manner. Kozoriz, M.G., Kuzmiski, J.B., Hirasawa, M., Pittman, Q.J. J. Neurophysiol. (2006) [Pubmed]
  5. No overlap of sensitivity to capsaicin and expression of galanin in rat dorsal root ganglion neurons after axotomy. Wendland, J.R., Schmidt, K.H., Koltzenburg, M., Petersen, M. Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale. (2003) [Pubmed]
  6. Molecular cloning and characterization of a new receptor for galanin. Howard, A.D., Tan, C., Shiao, L.L., Palyha, O.C., McKee, K.K., Weinberg, D.H., Feighner, S.D., Cascieri, M.A., Smith, R.G., Van Der Ploeg, L.H., Sullivan, K.A. FEBS Lett. (1997) [Pubmed]
  7. Long-term plastic changes in galanin innervation in the rat basal forebrain. Hartonian, I., Mufson, E.J., De Lacalle, S. Neuroscience (2002) [Pubmed]
  8. Six-hour selective REM sleep deprivation increases the expression of the galanin gene in the hypothalamus of rats. Fujihara, H., Serino, R., Ueta, Y., Sei, H., Morita, Y. Brain Res. Mol. Brain Res. (2003) [Pubmed]
  9. Galanin and perseveration. Echevarria, D.J., Brewer, A., Bushell, G., Manuzon, H., Langel, U., Robinson, J.K. Brain Res. (2005) [Pubmed]
  10. Regulation by osmotic stimuli of galanin-R1 receptor expression in magnocellular neurones of the paraventricular and supraoptic nuclei of the rat. Burazin, T.C., Larm, J.A., Gundlach, A.L. J. Neuroendocrinol. (2001) [Pubmed]
  11. Galanin Protects Amyloid-beta-Induced Neurotoxicity on Primary Cultured Hippocampal Neurons of Rats. Cheng, Y., Yu, L.C. J. Alzheimers. Dis. (2010) [Pubmed]
  12. Differential role of galanin receptors in the regulation of depression-like behavior and monoamine/stress-related genes at the cell body level. Kuteeva, E., Wardi, T., Lundström, L., Sollenberg, U., Langel, U., Hökfelt, T., Ogren, S.O. Neuropsychopharmacology. (2008) [Pubmed]
  13. Anxiolytic- and antidepressant-like profiles of the galanin-3 receptor (Gal3) antagonists SNAP 37889 and SNAP 398299. Swanson, C.J., Blackburn, T.P., Zhang, X., Zheng, K., Xu, Z.Q., Hökfelt, T., Wolinsky, T.D., Konkel, M.J., Chen, H., Zhong, H., Walker, M.W., Craig, D.A., Gerald, C.P., Branchek, T.A. Proc. Natl. Acad. Sci. U. S. A. (2005) [Pubmed]
  14. Neuropeptide expression in rats exposed to chronic mild stresses. Sergeyev, V., Fetissov, S., Mathé, A.A., Jimenez, P.A., Bartfai, T., Mortas, P., Gaudet, L., Moreau, J.L., Hökfelt, T. Psychopharmacology. (Berl). (2005) [Pubmed]
  15. Behavioral reactivity to stress: amplification of stress-induced noradrenergic activation elicits a galanin-mediated anxiolytic effect in central amygdala. Khoshbouei, H., Cecchi, M., Dove, S., Javors, M., Morilak, D.A. Pharmacol. Biochem. Behav. (2002) [Pubmed]
  16. Galanin-mediated anxiolytic effect in rat central amygdala is not a result of corelease from noradrenergic terminals. Barrera, G., Hernandez, A., Poulin, J.F., Laforest, S., Drolet, G., Morilak, D.A. Synapse. (2006) [Pubmed]
  17. Chronic social stress increases levels of preprogalanin mRNA in the rat locus coeruleus. Holmes, P.V., Blanchard, D.C., Blanchard, R.J., Brady, L.S., Crawley, J.N. Pharmacol. Biochem. Behav. (1995) [Pubmed]
  18. Demonstration of an extensive trans-tubular network continuous with the Golgi apparatus stack that may function in glycosylation. Roth, J., Taatjes, D.J., Lucocq, J.M., Weinstein, J., Paulson, J.C. Cell (1985) [Pubmed]
  19. Galactose and N-acetylgalactosamine-specific endocytosis of glycopeptides by isolated rat hepatocytes. Baenziger, J.U., Fiete, D. Cell (1980) [Pubmed]
  20. Attenuation of seizures and neuronal death by adeno-associated virus vector galanin expression and secretion. Haberman, R.P., Samulski, R.J., McCown, T.J. Nat. Med. (2003) [Pubmed]
  21. Galanin regulates basal and oestrogen-stimulated lactotroph function. Wynick, D., Hammond, P.J., Akinsanya, K.O., Bloom, S.R. Nature (1993) [Pubmed]
  22. Response of hypothalamic peptide mRNAs to thyroidectomy. Ceccatelli, S., Giardino, L., Calzá, L. Neuroendocrinology (1992) [Pubmed]
  23. Galanin as a physiological neurotransmitter in hemodynamic control of arginine vasopressin release in rats. Kondo, K., Murase, T., Otake, K., Ito, M., Kurimoto, F., Oiso, Y. Neuroendocrinology (1993) [Pubmed]
  24. The galanin-R2 agonist AR-M1896 reduces glutamate toxicity in primary neural hippocampal cells. Pirondi, S., Fernandez, M., Schmidt, R., Hökfelt, T., Giardino, L., Calzà, L. J. Neurochem. (2005) [Pubmed]
  25. Pertussis toxin-sensitive G-protein mediates galanin's inhibition of scopolamine-evoked acetylcholine release in vivo and carbachol-stimulated phosphoinositide turnover in rat ventral hippocampus. Consolo, S., Bertorelli, R., Girotti, P., La Porta, C., Bartfai, T., Parenti, M., Zambelli, M. Neurosci. Lett. (1991) [Pubmed]
  26. Characterization of a high-affinity galanin receptor in the rat anterior pituitary: absence of biological effect and reduced membrane binding of the antagonist M15 differentiate it from the brain/gut receptor. Wynick, D., Smith, D.M., Ghatei, M., Akinsanya, K., Bhogal, R., Purkiss, P., Byfield, P., Yanaihara, N., Bloom, S.R. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  27. Tissue-specific expression of the rat galanin gene. Kaplan, L.M., Spindel, E.R., Isselbacher, K.J., Chin, W.W. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  28. Distribution of messenger RNAs encoding enkephalin, substance P, somatostatin, galanin, vasoactive intestinal polypeptide, neuropeptide Y, and calcitonin gene-related peptide in the midbrain periaqueductal grey in the rat. Smith, G.S., Savery, D., Marden, C., López Costa, J.J., Averill, S., Priestley, J.V., Rattray, M. J. Comp. Neurol. (1994) [Pubmed]
  29. Role of galanin receptor 1 in gastric motility in rat. Guerrini, S., Raybould, H.E., Anselmi, L., Agazzi, A., Cervio, E., Reeve, J.R., Tonini, M., Sternini, C. Neurogastroenterol. Motil. (2004) [Pubmed]
  30. Galanin receptors in the hippocampus and entorhinal cortex of aged Fischer 344 male rats. Planas, B., Kolb, P.E., Raskind, M.A., Miller, M.A. Neurobiol. Aging (1998) [Pubmed]
  31. Galanin inhibits tyrosine hydroxylase expression in midbrain dopaminergic neurons. Counts, S.E., McGuire, S.O., Sortwell, C.E., Crawley, J.N., Collier, T.J., Mufson, E.J. J. Neurochem. (2002) [Pubmed]
  32. The differences in structural specificity for recognition and binding between asialoglycoprotein receptors of liver and macrophages. Ozaki, K., Lee, R.T., Lee, Y.C., Kawasaki, T. Glycoconj. J. (1995) [Pubmed]
  33. Identification and analysis of a CA(2+)-dependent lactoferrin receptor in rat liver. Lactoferrin binds to the asialoglycoprotein receptor in a galactose-independent manner. McAbee, D.D., Bennatt, D.J., Ling, Y.Y. Adv. Exp. Med. Biol. (1998) [Pubmed]
  34. Subunit composition of G(o) proteins functionally coupling galanin receptors to voltage-gated calcium channels. Kalkbrenner, F., Degtiar, V.E., Schenker, M., Brendel, S., Zobel, A., Heschler, J., Wittig, B., Schultz, G. EMBO J. (1995) [Pubmed]
  35. Large calibre primary afferent neurons projecting to the gracile nucleus express neuropeptide Y after sciatic nerve lesions: an immunohistochemical and in situ hybridization study in rats. Zhang, X., Meister, B., Elde, R., Verge, V.M., Hökfelt, T. Eur. J. Neurosci. (1993) [Pubmed]
  36. Regulation of galanin in memory pathways. Miller, M.A. Ann. N. Y. Acad. Sci. (1998) [Pubmed]
  37. Expression and sexual dimorphism of galanin messenger ribonucleic acid in growth hormone-releasing hormone neurons of the rat during development. Delemarre-van de Waal, H.A., Burton, K.A., Kabigting, E.B., Steiner, R.A., Clifton, D.K. Endocrinology (1994) [Pubmed]
  38. Ultrastructural studies on peptides in the dorsal horn of the spinal cord--I. Co-existence of galanin with other peptides in primary afferents in normal rats. Zhang, X., Nicholas, A.P., Hökfelt, T. Neuroscience (1993) [Pubmed]
  39. Axon terminals containing tyrosine hydroxylase- and dopamine-beta-hydroxylase immunoreactivity form synapses with galanin immunoreactive neurons in the lateral division of the bed nucleus of the stria terminalis in the rat. Kozicz, T. Brain. Res. (2001) [Pubmed]
  40. Estrogen and estrogen receptor-{beta} (ER{beta})-selective ligands induce galanin expression within gonadotropin hormone-releasing hormone-immunoreactive neurons in the female rat brain. Merchenthaler, I., Hoffman, G.E., Lane, M.V. Endocrinology (2005) [Pubmed]
  41. Galanin reduces PDBu-induced protein phosphorylation in rat ventral hippocampus. La Porta, C., Bianchi, R., Sozzani, S., Bartfai, T., Consolo, S. FEBS Lett. (1992) [Pubmed]
  42. Central galanin stimulates pituitary prolactin secretion in rats: possible involvement of hypothalamic vasoactive intestinal polypeptide. Koshiyama, H., Kato, Y., Inoue, T., Murakami, Y., Ishikawa, Y., Yanaihara, N., Imura, H. Neurosci. Lett. (1987) [Pubmed]
  43. Galanin receptor antagonists decrease fat preference in Brattleboro rat. Odorizzi, M., Fernette, B., Angel, E., Burlet, C., Tankosic, P., Burlet, A. Neuropharmacology (2002) [Pubmed]
  44. Peptide-containing nerve fibers in the parathyroid glands of different species. Luts, L., Sundler, F. Regul. Pept. (1994) [Pubmed]
  45. Young Adult-Specific Hyperphagia in Diabetic Goto-Kakizaki Rats is Associated with Leptin Resistance and Elevation of Neuropeptide Y mRNA in the Arcuate Nucleus. Maekawa, F., Fujiwara, K., Kohno, D., Kuramochi, M., Kurita, H., Yada, T. J. Neuroendocrinol. (2006) [Pubmed]
  46. Quantification of axotomy-induced alteration of neuropeptide mRNAs in dorsal root ganglion neurons with special reference to neuropeptide Y mRNA and the effects of neonatal capsaicin treatment. Noguchi, K., De León, M., Nahin, R.L., Senba, E., Ruda, M.A. J. Neurosci. Res. (1993) [Pubmed]
  47. Galanin-R1 and -R2 receptor mRNA expression during the development of rat brain suggests differential subtype involvement in synaptic transmission and plasticity. Burazin, T.C., Larm, J.A., Ryan, M.C., Gundlach, A.L. Eur. J. Neurosci. (2000) [Pubmed]
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