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  • Gal is a amino acid

    2021-09-15

    Gal is a 29-amino CFTRinh-172 residue peptide, comprising 30 amino acids in humans, isolated from the porcine intestine 30 years ago (Tatemoto et al., 1983). It has been shown to be involved in the regulation of numerous processes, including neuroendocrine control of systems such as the hypothalamic–pituitary–adrenal axis as well as feeding, intestine secretion, nerve regeneration, learning, memory or nociception (Butzkueven, Gundlach, 2010, Gundlach, 2002, Lang et al, 2007, Ogren et al, 2010, Shen, Gundlach, 2010, Tortorella et al, 2007). Gal was structurally unrelated to any known peptide in the mammalian brain. Today the galanin peptide family consists of the “parental” Gal, galanin-like peptide (GALP), galanin-message-associated peptide (GMAP) and a recently-discovered peptide named “alarin” (Lang et al., 2007). Gal functions are mediated by at least three galanin receptor subtypes (GAL1, GAL2, and GAL3) which belong to G protein-coupled receptors (GPCRs) (Branchek et al., 2000). Galanin and galanin receptor-binding sites are widely distributed within CNS, but historically much research has been focused on hypothalamic galanin systems including those in the preoptic area, paraventricular nucleus, supraoptic nucleus, and arcuate nucleus (ARC) (Gundlach et al, 2001, Mennicken et al, 2002, Waters, Krause, 2000). Most galanin-immunoreactive neurons (Gal-ir) in SON and PVN project directly to the posterior lobe of the pituitary, indicating that galanin may play a role in the modulation of hypophyseal secretion (Arai et al., 1990). Immunohistochemical and in vitro studies have confirmed the coexistence of Gal with AVP in the rat hypothalamic magnocellular neurons in the SON and PVN (mPVN) and/or pPVN (Bartfai, 1995, Gai et al, 1990, Gundlach, Burazin, 1998, Meister et al, 1990, Sanchez et al, 2001). While studying the role of galanin in the modulation of the release of neurohypophysial hormones, Ciosek and co-workers reported that galanin affects vasopressin and oxytocin release from the hypothalamo-neurohypophysial system in hemorrhaged, dehydrated or salt-loaded rats. This increase in plasma vasopressin and oxytocin during hemorrhaging was inhibited in rats previously treated intracerebroventricularly (icv) with galanin (Ciosek et al., 2003). Gal acts as an inhibitory neuromodulator of AVP and OT secretion in rats experiencing a hemorrhage or those which are dehydrated or salt loaded (Ciosek, Cisowska, 2003, Ciosek et al, 2003, Cisowska-Maciejewska, Ciosek, 2005). An in vitro study by Izdebska and Ciosek (2010) showed that a range of Gal concentrations exerted an inhibitory effect on the AVP secretion of all incubated tissues as well as on OT release from the neurohypophysis and hypothalamo-neurohypophysial explants. Recently, Ciosek and Drobnik (2013) demonstrated that Gal acts as a stimulatory neuromodulator of OT release in vitro in response to prolonged osmotic stimulus and that, conversely, acute osmotic stimulus blocks OT-ergic neurons susceptible to Gal. Galanin-like peptide, the second member of the galanin peptide family, was discovered while searching for additional ligands capable of activating galanin receptors (Ohtaki et al., 1999). GALP was identified as a 60-amino-acid peptide, which, unlike Gal, has a non-amidated C-terminus. GALP shares sequence homology to galanin (1–13) in positions 9–21 and can activate three galanin receptor subtypes (GAL1-3) with a preference for GAL2 and GAL3 over GAL1 (Lang et al., 2005). A second region, highly conserved between different species, is unique to the GALP peptide and lies between residues 38–54. It is hypothesized to be a binding region for a putative GALP-specific receptor (Man, Lawrence, 2008, Robinson et al, 2006), which is as yet unknown. In contrast to the broad distribution of Gal in the central nervous system, GALP mRNA was not detected in magnocellular neurons of the supraoptic or paraventricular nucleus (Shen et al., 2001). GALP mRNA and protein are expressed only in the neurons of the hypothalamic ARC, the median eminence, and in the pituicytes of the posterior pituitary, specialized astrocytes that are thought to modulate posterior pituitary hormone release by changing the amount of contacts between axon terminals and fenestrated capillaries (Kerr et al., 2000). GALP neurons in the ARC receive neuropeptide-Y (NPY) projections and more than 85% of these neurons express leptin receptor (Takatsu et al., 2001). There is lack of GALP mRNA in the magnocellular neurons of the paraventricular and supraoptic nuclei, which supply the majority of neuronal projections into the neurohypophysis (Shen et al., 2001). However, dense staining of GALP-containing fibers was found in the anterior parvicellular part of the PVN (pPVN) (Takatsu et al., 2001).