Galanin

Galanin was first identified from porcine intestinal extracts in 1978 by Professor Viktor Mutt and colleagues at the Karolinska Institute, Sweden using a chemical assay technique that detects peptides according to its C-terminal alanine amide structure. Galanin is so-called because it contains an N-terminal glycine residue and a C-terminal alanine. The structure of galanin was determined in 1983 by the same team, and the cDNA of galanin was cloned from a rat anterior pituitary library in 1987. ==Tissue distribution==

Galanin is located predominantly in the central nervous system and gastrointestinal tract. Within the central nervous system, highest concentrations are found in the hypothalamus, with lower levels in the cortex and brainstem. In the hypothalamus, it is for example found in the ventrolateral preoptic nucleus where it has sleep-promoting function. Within the brain, galanin has also been found in the ventral forebrain and amygdala. Along with this, the immune reaction of galanin in the brain is centered in the hypothalamopituitary. Gastrointestinal galanin is most abundant in the duodenum, with lower concentrations in the stomach, small intestine, and colon. Specifically, it has been found in keratinocytes, eccrine sweat glands, and around blood vessels. Within gastric cancer cells, galanin has been found to have a tumor suppressive role, but hypermethylation has been shown to stop its tumor suppressive properties. == Structure ==

Galanin is a peptide consisting of a chain of 29 amino acids (30 amino acids in humans) produced from the cleavage of a 123-amino acid protein known as prepro galanin, which is encoded by the GAL gene. The sequence of this gene is highly conserved among mammals, showing over 85% homology between rat, mouse, porcine, bovine, and human sequences. In these animal forms, the first 15 amino acids from the N-terminus are identical, but amino acids differ at several positions on the C-terminal end of the protein. Even though the protein structures are very similar, they often have very different effects in different animals. For example, porcine and rat galanin inhibit glucose-induced insulin secretion in rats and dogs but have no effect on insulin secretion in humans. This demonstrates that it is essential to study the effects of galanin and other regulatory peptides in their autologous species. The galanin family of protein consists of four proteins, of which GAL was the first to be identified. The second was galanin message-associated protein (GMAP), a 59- or 60-amino acid peptide also formed from the cleavage of prepro galanin. The other two peptides, galanin-like peptide (GALP) and alarin, were identified relatively recently and are both encoded for in the same gene, the prepro GALP gene. GALP and alarin are produced by different post-transcriptional splicing of this gene. ==Receptors==

Galanin signalling occurs through three classes of receptors, GALR1, GALR2, and GALR3, which are all part of the G protein-coupled receptor (GPCR) superfamily. Galanin receptors are expressed in the central nervous system, in the pancreas, and on solid tumours. The level of expression of the different receptors varies at each location, and this distribution changes after injury to neurons. Experiments into the function of the receptor subtypes involve mostly genetic knockout mice. The location of the receptor and the combination of receptors that are inhibited or stimulated heavily affect the outcome of galanin signalling. ==Clinical characteristics==

Appetite Injections of galanin into the lateral ventricle or directly into the hypothalamus of rats creates the urge to feed, with a preference for eating fats. Galanin is an inhibitor of pancreatic secretion of insulin. It is involved in repeated alcohol intake. Endocrine Galanin inhibits the secretion of insulin and somatostatin and stimulates the secretion of glucagon, prolactin, somatotropin, adrenocorticotropin, luteinizing hormone, foliculotropin, growth hormone-releasing hormone, hypothalamic gonadotropin-releasing hormone, and corticotropin-releasing hormone. Epilepsy Galanin in the hippocampus is an inhibitor of glutamate but not of GABA. This means that galanin is capable of increasing the seizure threshold with high doses having been shown to reduce pain. Along with this, galanin is believed to be effective in reducing spinal hyperexcitability. == See also ==