Trends in Pharmacological Sciences
ReviewGalanin receptor subtypes
Section snippets
Native galanin receptors
The first binding profiles derived from native systems with galanin and related peptide analogues (Fig. 1) were consistent with multiple receptor subtypes4, 6, 7, 8, although definitive proof required cloning. Peptides displaced [125I]galanin binding to human Bowes melanoma cell membranes with a distinctive order of potency: galanin-1–30 > galanin-1–16 > d-Trp2-galanin ⪢ galanin-3–30 (Ref. 9). [125I]galanin binding sites with a difference in affinity of up to a factor of ten for galanin and
The GAL1 receptor
The first known galanin receptor GAL1 has been isolated from the human Bowes melanoma cell line34 and other sources35, 36. Human GAL1 contains 349 amino acids with the structure of a G-protein-coupled receptor (GPCR)37. The highest amino acid similarities are found with human gal2 (42%) and human gal3 (38%) receptors, the rat orphan receptor GPR54 (37%)38, and human somatostatin and opioid receptors (30–34%)39. A rat GAL1 homologue, cloned from brain40 and RIN-14b cells39, 41, contains 346
In vivo responses to galanin: comparison with cloned receptors
The effects of galanin in vivo have been studied extensively3, 5; experimental paradigms include modulation of acetylcholine release, memory and Alzheimer’s disease71, 72, feeding behaviour73, pain3, depression3, gut secretion and motility74, cardiovascular tone75, cerebrovascular tone76, neuroendocrine regulation, lacation and reproduction77 and neuroregeneration78. An in-depth discussion of these effects is beyond the scope of this review; the few models selected here are not comprehensive
Concluding remarks
It is clear that there is a lack of concordance of profiles for cloned galanin receptor subtypes with the effects of galanin-like peptides in native systems. The cloned receptors do not readily account for the reported antagonist actions of the chimeric peptides M15, M32, M35, C7 and especially M40, nor do they account for responses to galanin-3–29. Furthermore, the cloned receptors do not account for the enhanced potency or opposing actions of galanin-1-15 compared with full-length galanin.
Acknowledgements
We thank George Moralishvili for expert graphic assistance.
Glossary
Chemical names
- M15:
- galanin-1–13-substance-P-5–11 amide, also known as galantide
- M32:
- galanin-1–13-NPY25–36 amide
- M35:
- galanin-1–13-bradykinin-2–9 amide
- M40:
- galanin-1–13-Pro-Pro-Ala-Leu-Ala-Leu-Ala amide
- C7:
- galanin-1–13-spantide amide, substance P receptor antagonist
- SCH202596:
- 2-[(5-methoxy-3-oxo-1-carboxymethyl)-6-spiro(1,4-cyclohexadienyl)]-(3S,4S,5S,6S)-6-[(5,7-dichloro-6-methyl-3-oxo-2,3-dihydrobenzo[b]furan-4-yl)oxyl]-3,4,5-trihydroxy-1-cyclohexene-1-methylcarboxylate
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