Galanin receptors and their therapeutic potential

Abstract

Galanin, a 29 - 30 amino acid neuropeptide, is widely distributed in both the central and peripheral nervous systems. The peptide is unique to other families of neuropeptides and is highly conserved in the N-terminal portion among several mammalian species. Cloning efforts have successfully yielded three galanin receptor (GalR) subtypes that have high affinities for galanin. A recently isolated galanin-like peptide has high affinity for at least one of the three receptors. Galanin modulates a variety of physiological processes via activation of these receptor subtypes. In the CNS, galanin alters the release of several neurotransmitters. For example, it has an inhibitory effect on the release of acetylcholine (ACh) in the hippocampus, suggesting a potential role in the modulation of memory and learning. When injected directly into the ventricles of the brain, galanin increases food intake and alters plasma levels of hormones involved in the maintenance of nutrient and body weight homeostasis. The peptide also has modulatory effects on the perception of pain (nociception). Galanin stimulates release of growth hormone (GH), prolactin and luteinising hormone (LH) from the pituitary. In the periphery, galanin inhibits insulin secretion from pancreatic β-cells and contracts or relaxes various gastrointestinal smooth muscles. Thus, there is the potential for drug development in several therapeutic areas including nociception, anxiety, depression, obesity, memory disorders, diabetes, cardiovascular disease, digestive disorders, sexual dysfunction and growth disorders. As a result, GalRs have become popular drug targets for the pharmaceutical and biotechnological industries. Screening for galanin receptor agonists and antagonists has been initiated using high-throughput assays against the identified receptors. It is hoped that identification of small, non-peptide, selective and highly potent molecules may bring new therapeutic identities for these disease states that currently lack effective treatments. Meanwhile, these molecules may be employed as research tools, along with others, to provide proof of principle and validation of GalRs as drug targets.

• cognition
• compound screening
• food intake
• G-protein coupled receptor
• galanin
• nociception
• obesity
• psychiatric disorders
• receptor pharmacology
• signal transduction
• therapeutic drugs