Tuesday, August 18, 2009

Galanins and Galanin Message Associated Peptide (GMAP) Fragments

Galanin (GAL) is a neuropeptide found in both the central and peripheral nervous systems. It is involved in normal growth and development of the nervous system and is critically important for the recovery of nerve function after nerve injury1.

Related Peptides
The mRNA encoding the galanin is composed of a 5’ portion encoding a signal sequence, followed by a Lys-Arg cleavage site, then the 29-amino-acid-long galanin peptide followed by Gly-Lys-Arg at the C-terminal containing the amide donor Gly and the cleavage site Lys-Arg. The galanin-encoding portion of the mRNA is followed by 180 bases encoding a 60-amino-acid-long peptide, named the galanin-message-associated peptide (GMAP). Galanin message-associated peptide (GMAP) is a flanking peptide in mammalian preprogalanin located C-terminally of galanin (GAL). GMAP is generally colocalized with galanin in the central nervous system as well as the peripheral nervous system2.

Galanin was first isolated from porcine intestine in 1983 and was soon later identified in other tissues including the CNS. Subsequently the human galanin gene was cloned in 19883.

Structural Characteristics
Human Galanin consists of 30 amino acids, with a free carboxylic acid on the C-terminus, whereas all other known types of galanin are composed of 29 amino acids with a C-terminus amide.

Mode of action
Galanin primarily exerts its effects through G-protein coupled receptors. Galanin is capable of opening K+ channels and hyperpolarizing neurons, inhibiting adenylate cyclase activity, inhibiting voltage-gated Ca2+ channels, inhibiting phosphoinositide turnover, and regulating the release of dopamine, noradrenaline, acetylcholine, and glutamate. The regulation of transmitter release is an important mechanism by which galanin could potentially modulate neuronal function. Galanin acts through multiple presynaptic receptors to inhibit the release process4.

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 learning5. Galanin appears to regulate both fat and glucose levels by altering 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 ß-cells and contracts or relaxes various gastrointestinal smooth muscles6.

1.Tatemoto K, Rökaeus A, Jörnvall H, McDonald TJ, Mutt V (1983). Galanin - a novel biologically active peptide from porcine intestine. FEBS Lett., 28, 164(1), 124-8.
2.Bartfai T (1995). Galanin: A neuropeptide with important CNS actions. In: Psychopharmacology: The Fourth Generation of Progress (F.E. Bloom and D.J. Kupfer, eds.) Raven Press, Ltd., New York, pp 563-571 (1995)
3.Book: Handbook of biologically active peptides. By Abba J. Kastin
4.Kinney GA, Emmerson PJ and Miller RJ (1998). Galanin Receptor-Mediated Inhibition of Glutamate Release in the Arcuate Nucleus of the Hypothalamus. J Neuroscience, 18(10), 3489-3500
5.Xu XJ, Andell S, Bartfai T, Wiesenfeld-Hallin Z (1996). Fragments of galanin message-associated peptide (GMAP) modulate the spinal flexor reflex in rat. European J Pharmacology, 318(2-3), 301-6.
6.Wang S ?, Hwa J?, Varty G (2000). Galanin receptors and their therapeutic potential. Expert Opinion on Emerging Drugs, 5(4), 415-440.

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