Galanin receptors (provisional nomenclature as recommended by NC-IUPHAR [8]) are activated by the endogenous peptides galanin (GAL, P22466) and galanin-like peptide (GALP, Q9UBC7). Human galanin (GAL, P22466) is a 30 amino-acid non-amidated peptide [6]; in other species, it is 29 amino acids long and C-terminally amidated. Amino acids 1-14 of galanin are highly conserved in mammals, birds, reptiles, amphibia and fish. Shorter peptide species (e.g. human galanin-1-19 [3] and porcine galanin-5-29 [23]) and N-terminally extended forms (e.g. N-terminally seven and nine residue elongated forms of porcine galanin [4,23]) have been reported. More recently, the newly-identified peptide, spexin (SPX), has been reported to activate human GAL2 and GAL3 (but not GAL1) receptors in heterologous expression systems; and to alter GAL2/3 receptor-related behaviours in animals [10].

Galanin-(1-11) is a high-affinity agonist at GAL₁/GAL₂ (pK_i 9), and galanin(2-11) is selective for GAL₂ and GAL₃ compared with GAL₁ [16]. [¹²⁵I]-[Tyr²⁶]galanin binds to all three subtypes with K_d values generally reported to range from 0.05 to 1 nM, depending on the assay conditions used [7,24-26,31]. Porcine galanin-(3-29) does not bind to cloned GAL₁, GAL₂ or GAL₃ receptors, but a receptor that is functionally activated by porcine galanin-(3–29) has been reported in pituitary and gastric smooth muscle cells [9,34]. Additional galanin receptor subtypes are also suggested from studies with chimeric peptides (e.g. M15, M35 and M40), which act as antagonists in functional assays in the cardiovascular system [29], spinal cord [33], locus coeruleus, hippocampus [1] and hypothalamus [2,15], but exhibit agonist activity at some peripheral sites [2,9]. The chimeric peptides M15, M32, M35, M40 and C7 are agonists at GAL₁ receptors expressed endogenously in Bowes human melanoma cells [18], and at heterologously expressed recombinant GAL₁, GAL₂ and GAL₃ receptors [7,25-26]. Further studies described the synthesis of a series of novel, systemically-active, galanin analogues, with modest preferential binding at the GAL₂ receptor. Specific chemical modifications to the galanin backbone increased brain levels of these peptides after i.v. injection and several of these peptides exerted a potent antidepressant-like effect in mouse models of depression [21]. More recent studies have identified synthetic spexin (SPX)-based peptides that are selective GAL₂ receptor agonists [14,20].

* Key recommended reading is highlighted with an asterisk

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* Foord SM, Bonner TI, Neubig RR, Rosser EM, Pin JP, Davenport AP, Spedding M, Harmar AJ. (2005) International Union of Pharmacology. XLVI. G protein-coupled receptor list. Pharmacol Rev, 57 (2): 279-88. [PMID:15914470]

Hokfelt T (Ed). (2010) Galanin. Experientia Supplementum Springer, AG, Basel, 102: 208.

* Lang R, Gundlach AL, Holmes FE, Hobson SA, Wynick D, Hökfelt T, Kofler B. (2015) Physiology, signaling, and pharmacology of galanin peptides and receptors: three decades of emerging diversity. Pharmacol Rev, 67 (1): 118-75. [PMID:25428932]

Lang R, Gundlach AL, Kofler B. (2007) The galanin peptide family: receptor pharmacology, pleiotropic biological actions, and implications in health and disease. Pharmacol Ther, 115 (2): 177-207. [PMID:17604107]

* Lang R, Kofler B. (2011) The galanin peptide family in inflammation. Neuropeptides, 45 (1): 1-8. [PMID:21087790]

* Lawrence C, Fraley GS. (2011) Galanin-like peptide (GALP) is a hypothalamic regulator of energy homeostasis and reproduction. Front Neuroendocrinol, 32 (1): 1-9. [PMID:20558195]

Man PS, Lawrence CB. (2008) Galanin-like peptide: a role in the homeostatic regulation of energy balance?. Neuropharmacology, 55 (1): 1-7. [PMID:18538801]

Mitsukawa K, Lu X, Bartfai T. (2008) Galanin, galanin receptors and drug targets. Cell Mol Life Sci, 65 (12): 1796-805. [PMID:18500647]

Moreno E, Vaz SH, Cai NS, Ferrada C, Quiroz C, Barodia SK, Kabbani N, Canela EI, McCormick PJ, Lluis C et al.. (2011) Dopamine-galanin receptor heteromers modulate cholinergic neurotransmission in the rat ventral hippocampus. J Neurosci, 31 (20): 7412-23. [PMID:21593325]

Ogren SO, Kuteeva E, Elvander-Tottie E, Hökfelt T. (2010) Neuropeptides in learning and memory processes with focus on galanin. Eur J Pharmacol, 626 (1): 9-17. [PMID:19837050]

* Webling KE, Runesson J, Bartfai T, Langel U. (2012) Galanin receptors and ligands. Front Endocrinol (Lausanne), 3: 146. [PMID:23233848]

Wraith DC, Pope R, Butzkueven H, Holder H, Vanderplank P, Lowrey P, Day MJ, Gundlach AL, Kilpatrick TJ, Scolding N et al.. (2009) A role for galanin in human and experimental inflammatory demyelination. Proc Natl Acad Sci USA, 106 (36): 15466-71. [PMID:19717462]

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Subcommittee members: Andrew L. Gundlach (Chairperson) Florey Institute of Neuroscience and Mental Health The University of Melbourne Victoria 3010 Australia

Other contributors: Philip J. Ryan The Florey Neuroscience Institute of Neuroscience and Mental Health The University of Melbourne Victoria 3010 Australia