Galanin

Overview: Galanin receptors (provisional nomenclature, see Foord et al., 2005) are activated by the endogenous peptides galanin (ENSG00000069482) and galanin-like peptide (GALP, ENSG00000105099). Human galanin is a 30 amino-acid non-amidated peptide (Evans and Shine, 1991); 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, (Bersani et al., 1991a) and porcine galanin-5–29 (Sillard et al., 1992) and N-terminally extended forms [e.g. N-terminally seven and nine residue elongated forms of porcine galanin (Bersani et al., 1991b; Sillard et al., 1992)] have been reported.

Nomenclature	GAL1	GAL2	GAL3
Other names	Galanin-1 receptor, GALR1	Galanin-2 receptor, GALR2	Galanin-3 receptor, GALR3
Ensembl ID	ENSG00000166573	ENSG00000182687	ENSG00000128310
Principal transduction	Gi/o	Gi/o, Gq/11	Gi/o
Rank order of potency	Galanin > GALP (Ohtaki et al., 1999)	GALP ≥ galanin (Ohtaki et al., 1999)	GALP > galanin (Lang et al., 2005)
Selective agonists	–	Galanin-(2–29) (Fathi et al., 1997; Wang et al., 1997), D-Trp2-galanin-(1–29) (Smith et al., 1997)	–
Selective antagonists	2,3-Dihydro-dithiin and -dithiepine-1,1,4,4-tetroxides (Scott et al., 2000)	M871 (7.9, Sollenberg et al., 2006)	–

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 (Lu et al., 2005). [¹²⁵I]-[Tyr²⁶]galanin binds to all three subtypes with K_d values ranging from 0.05 to 1 nM (Skofitsch et al., 1986; Smith et al., 1997; 1998; Wang et al., 1997; Fitzgerald et al., 1998). 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 (Wynick et al., 1993; Gu et al., 1995). 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 (Ulman et al., 1993), spinal cord (Wiesenfeld-Hallin et al., 1992), locus coeruleus, hippocampus (Bartfai et al., 1991) and hypothalamus (Leibowitz and Kim, 1992; Bartfai et al., 1993), but exhibit agonist activity at some peripheral sites (Bartfai et al., 1993; Gu et al., 1995). The chimeric peptides M15, M32, M35, M40 and C7 are agonists at GAL₁ receptors expressed endogenously in Bowes human melanoma cells (Ohtaki et al., 1999), and at heterologously expressed recombinant GAL₁, GAL₂ and GAL₃ receptors (Smith et al., 1997; Fitzgerald et al., 1998; Smith et al., 1998).

Glossary

Abbreviations:

C7

galanin-(1–13)-spantide

M15

galanin-(1–13)-substance P-5–11 amide, also known as galantide

M32

galanin-(1–13)-neuropeptide Y amide-(25–36) amide

M35

galanin-(1–13)-bradykinin-(2–9) amide

M40

galanin-(1–13)-Pro-Pro-Ala-Leu-Ala-Leu-Ala-Leu-Ala amide

M871

galanin-(2–13)-Glu-His-(Pro)₃-(Ala-Leu)₂-Ala-amide

Further Reading

Bauer JW, Lang R, Jakab M, Kofler B (2008). Galanin family of peptides in skin function. Cell Mol Life Sci65: 1820–1825.

Foord SM, Bonner TI, Neubig RR, Rosser EM, Pin JP, Davenport AP et al. (2005). International Union of Pharmacology. XLVI. G protein-coupled receptor list. Pharmacol Rev57: 279–288.

Lang R, Gundlach AL, Kofler B (2007). The galanin peptide family: receptor pharmacology, pleiotropic biological actions, and implications in health and disease. Pharmacol Ther115: 177–207.

Man PS, Lawrence CB (2008). Galanin-like peptide: a role in the homeostatic regulation of energy balance? Neuropharmacology55: 1–7.

Mitsukawa K, Lu X, Bartfai T (2008). Galanin, galanin receptors and drug targets. Cell Mol Life Sci65: 1796–1805.

Ogren SO, Kuteeva E, Hokfelt T, Kehr J (2006). Galanin receptor antagonists: a potential novel pharmacological treatment for mood disorders. CNS Drugs20: 633–654.

Walton KM, Chin JE, Duplantier AJ, Mather RJ (2006). Galanin function in the central nervous system. Curr Opin Drug Discov Devel9: 560–570.