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      Review: Occurrence and Distribution of Galanin in the Physiological and Inflammatory States in the Mammalian Gastrointestinal Tract

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          Abstract

          Galanin (GAL) is a broad-spectrum peptide that was first identified 37 years ago. GAL, which acts through three specific receptor subtypes, is one of the most important molecules on an ever-growing list of neurotransmitters. Recent studies indicate that this peptide is commonly present in the gastrointestinal (GI) tract and GAL distribution can be seen in the enteric nervous system (ENS). The function of the GAL in the gastrointestinal tract is, inter alia, to regulate motility and secretion. It should be noted that the distribution of neuropeptides is largely dependent on the research model, as well as the part of the gastrointestinal tract under study. During the development of digestive disorders, fluctuations in GAL levels were observed. The occurrence of GAL largely depends on the stage of the disease, e.g., in porcine experimental colitis GAL secretion is caused by infection with Brachyspira hyodysenteriae. Many authors have suggested that increased GAL presence is related to the involvement of GAL in organ renewal. Additionally, it is tempting to speculate that GAL may be used in the treatment of gastroenteritis. This review aims to present the function of GAL in the mammalian gastrointestinal tract under physiological conditions. In addition, since GAL is undoubtedly involved in the regulation of inflammatory processes, and the aim of this publication is to provide up-to-date knowledge of the distribution of GAL in experimental models of gastrointestinal inflammation, which may help to accurately determine the role of this peptide in inflammatory diseases and its potential future use in the treatment of gastrointestinal disorders.

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          Most cited references100

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          Dextran sulfate sodium-induced colitis occurs in severe combined immunodeficient mice.

          Oral administration of dextran sulfate sodium (DSS) has been reported to induce colitis in mice. The purpose of this study was to determine whether the possible pathogenic mechanism involved the acquired immune system. Normal BALB/c and related C.B17 severe combined immunodeficient mice were fed 5% DSS (40 kilodaltons) in their drinking water for 7 days; controls were fed only water. Colons were scored for histological activity at various times. Cytokine production by cultures of colon and of draining lymph node cell was measured. The effect of DSS on the proliferation of the MCA-38 colonic epithelial cell line was assessed. DSS feeding resulted in a very reproducible acute distal colitis in both BALB/c and C.B17 severe combined immunodeficient mice. The lesions of BALB/c mice had an increased production of macrophage-derived cytokines, such as interleukin (IL) 1 beta, IL-6, tumor necrosis factor, and granulocyte-macrophage colony-stimulating factor, but not the T-cell cytokines IL-3 or interferon gamma. Draining lymph node cells produced these cytokines plus interferon gamma and IL-3. DSS inhibited MCA-38 cells at doses that would be easily achieved in the distal colon. Acute DSS-induced colitis does not require the presence of T cells or B cells because it occurred in C.B17 severe combined immunodeficient mice that lack these cells. Its induction may result from a toxicity of DSS for colonic epithelial cells.
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            Galanin - a novel biologically active peptide from porcine intestine.

            The isolation of a novel biologically active peptide, designated galanin, is described. The peptide was discovered by the detection of its C-terminal amide structure in porcine intestinal extract using a chemical method. It was found that galanin consists of 29 amino acids and the complete amino acid sequence is: Gly-Trp-Thr-Leu-Asn-Ser-Ala-Gly-Tyr-Leu-Leu-Gly-Pro-His-Ala-Ile-Asp-Asn-His -Arg-Ser -Phe-His-Asp-Lys-Tyr-Gly-Leu-Ala-NH2. Galanin was found to contract smooth muscle preparations from the rat and to cause a mild and sustained hyperglycemia in dog.
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              Physiology, signaling, and pharmacology of galanin peptides and receptors: three decades of emerging diversity.

              Galanin was first identified 30 years ago as a "classic neuropeptide," with actions primarily as a modulator of neurotransmission in the brain and peripheral nervous system. Other structurally-related peptides-galanin-like peptide and alarin-with diverse biologic actions in brain and other tissues have since been identified, although, unlike galanin, their cognate receptors are currently unknown. Over the last two decades, in addition to many neuronal actions, a number of nonneuronal actions of galanin and other galanin family peptides have been described. These include actions associated with neural stem cells, nonneuronal cells in the brain such as glia, endocrine functions, effects on metabolism, energy homeostasis, and paracrine effects in bone. Substantial new data also indicate an emerging role for galanin in innate immunity, inflammation, and cancer. Galanin has been shown to regulate its numerous physiologic and pathophysiological processes through interactions with three G protein-coupled receptors, GAL1, GAL2, and GAL3, and signaling via multiple transduction pathways, including inhibition of cAMP/PKA (GAL1, GAL3) and stimulation of phospholipase C (GAL2). In this review, we emphasize the importance of novel galanin receptor-specific agonists and antagonists. Also, other approaches, including new transgenic mouse lines (such as a recently characterized GAL3 knockout mouse) represent, in combination with viral-based techniques, critical tools required to better evaluate galanin system physiology. These in turn will help identify potential targets of the galanin/galanin-receptor systems in a diverse range of human diseases, including pain, mood disorders, epilepsy, neurodegenerative conditions, diabetes, and cancer. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                22 January 2021
                2020
                : 11
                : 602070
                Affiliations
                [1] Department of Clinical Physiology, Faculty of Veterinary Medicine, University of Warmia and Mazury , Olsztyn, Poland
                Author notes

                Edited by: Reinaldo B. Oria, Federal University of Ceara, Brazil

                Reviewed by: Manuel Narvaez Peláez, University of Malaga, Spain; Susanne Maria Brunner, Paracelsus Medical University, Austria

                *Correspondence: Marta Brzozowska, marta.czajkowska@ 123456uwm.edu.pl

                This article was submitted to Nutritional Immunology, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2020.602070
                7862705
                33552060
                14b19abb-56b9-423a-be97-8d3a2b1f82ee
                Copyright © 2021 Brzozowska and Całka

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 09 September 2020
                : 11 December 2020
                Page count
                Figures: 2, Tables: 3, Equations: 0, References: 100, Pages: 12, Words: 6197
                Funding
                Funded by: Ministerstwo Nauki i Szkolnictwa Wyższego 10.13039/501100004569
                Categories
                Immunology
                Review

                Immunology
                galanin,galanin receptors,inflammation,gastrointestinal tract,neuropeptide
                Immunology
                galanin, galanin receptors, inflammation, gastrointestinal tract, neuropeptide

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