Galanin Receptor Family

The galanin receptor (GALR) is a family of G protein-coupled receptor. It is a metabotropic receptor which binds galanin and was first discovered 30 years ago. The 29 amino acid long peptide (30 amino acids in humans) was named galanin after its N-terminal glycine and its C-terminal alanine. The N-terminal end of galanin, of which the first 15 amino acids are conserved in all species, is essential for its biological activity. However, the C-terminal region varies among species and lacks receptor affinity. The C-terminus is believed to primarily serve as a protector against proteolytic attacks.

Galanin receptors can be found throughout the peripheral and central nervous systems and the endocrine system. It co-exists with a number of classical neurotransmitters, including GABA, acetyl choline, noradrenalin, serotonin, glutamate, and dopamine. Selective galanin agonists are anticonvulsant, whereas antagonists produce antidepressant and anxiolytic effects in animals. Therefore, either agonist or antagonist ligands for the galanin receptors may be potentially therapeutic compounds for humans. An extensive up-regulation of galanin was observed both in PNS and CNS during sensory and motor system development and after nerve injury. GALR is also up-regulated in the basal forebrain of patients with Alzheimer’s disease. In addition, galanin has also been shown to be expressed in keratinocytes, eccrine sweat glands and around blood vessels.

Fig.1 The unknown signaling of the postulated galanin fragment preferring receptor (GalR1–GalR2 heteromer) is compared with the signaling of the GalR1 and GalR2 homomers. (Fuxe, 2012)

Here shows part of galanin receptor in humans including GAL-R1, GAL-R2, and GAL-R3, which are three subtypes of the receptor. All three belong to the GPCR superfamily but the subtypes have substantial differences in sites of expression as well as their functional coupling and subsequent signaling activities. These differences between the receptor subtypes contribute to the diversity of possible physiological effects as well as the plausible pharmacological relevance of targeting the galanin family.

Human Galanin Receptor Members
GALR1	GALR2	GALR3

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Reference

Fuxe K, et al. (2012). On the existence and function of galanin receptor heteromers in the central nervous system. Front Endocrinol (Lausanne). 3: 127.

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