Galanin receptors C
Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
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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].
Receptors
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GAL1 receptor
C
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GAL2 receptor
C
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GAL3 receptor
C
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Concise Guide to PHARMACOLOGY citation:
Alexander SPH, Christopoulos A, Davenport AP, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: G protein-coupled receptors. Br J Pharmacol. 180 Suppl 2:S23-S144.
Galanin-(1-11) is a high-affinity agonist at GAL1/GAL2 (pKi 9), and galanin(2-11) is selective for GAL2 and GAL3 compared with GAL1 [16]. [125I]-[Tyr26]galanin binds to all three subtypes with Kd 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].