title: Physiology, signaling, and pharmacology of galanin peptides and receptors: three decades of emerging diversity.
abstract: 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.
authors.affiliation: Department of Dermatology (R.L.) and Laura Bassi Centre of Expertise, Department of Pediatrics (B.K.), Paracelsus Private Medical University, Salzburg, Austria; The Florey Institute of Neuroscience and Mental Health, and Florey Department of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Victoria, Australia (A.L.G.); Schools of Physiology and Pharmacology and Clinical Sciences, Bristol University, Bristol, United Kingdom (F.E.H., S.A.H., D.W.); and Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden (T.H.).
authors.forename: Roland
authors.initials: R
authors.lastname: Lang
authors.affiliation: Department of Dermatology (R.L.) and Laura Bassi Centre of Expertise, Department of Pediatrics (B.K.), Paracelsus Private Medical University, Salzburg, Austria; The Florey Institute of Neuroscience and Mental Health, and Florey Department of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Victoria, Australia (A.L.G.); Schools of Physiology and Pharmacology and Clinical Sciences, Bristol University, Bristol, United Kingdom (F.E.H., S.A.H., D.W.); and Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden (T.H.).
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Gundlach
authors.affiliation: Department of Dermatology (R.L.) and Laura Bassi Centre of Expertise, Department of Pediatrics (B.K.), Paracelsus Private Medical University, Salzburg, Austria; The Florey Institute of Neuroscience and Mental Health, and Florey Department of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Victoria, Australia (A.L.G.); Schools of Physiology and Pharmacology and Clinical Sciences, Bristol University, Bristol, United Kingdom (F.E.H., S.A.H., D.W.); and Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden (T.H.).
authors.forename: Fiona E
authors.initials: FE
authors.lastname: Holmes
authors.affiliation: Department of Dermatology (R.L.) and Laura Bassi Centre of Expertise, Department of Pediatrics (B.K.), Paracelsus Private Medical University, Salzburg, Austria; The Florey Institute of Neuroscience and Mental Health, and Florey Department of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Victoria, Australia (A.L.G.); Schools of Physiology and Pharmacology and Clinical Sciences, Bristol University, Bristol, United Kingdom (F.E.H., S.A.H., D.W.); and Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden (T.H.).
authors.forename: Sally A
authors.initials: SA
authors.lastname: Hobson
authors.affiliation: Department of Dermatology (R.L.) and Laura Bassi Centre of Expertise, Department of Pediatrics (B.K.), Paracelsus Private Medical University, Salzburg, Austria; The Florey Institute of Neuroscience and Mental Health, and Florey Department of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Victoria, Australia (A.L.G.); Schools of Physiology and Pharmacology and Clinical Sciences, Bristol University, Bristol, United Kingdom (F.E.H., S.A.H., D.W.); and Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden (T.H.).
authors.forename: David
authors.initials: D
authors.lastname: Wynick
authors.affiliation: Department of Dermatology (R.L.) and Laura Bassi Centre of Expertise, Department of Pediatrics (B.K.), Paracelsus Private Medical University, Salzburg, Austria; The Florey Institute of Neuroscience and Mental Health, and Florey Department of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Victoria, Australia (A.L.G.); Schools of Physiology and Pharmacology and Clinical Sciences, Bristol University, Bristol, United Kingdom (F.E.H., S.A.H., D.W.); and Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden (T.H.).
authors.forename: Tomas
authors.initials: T
authors.lastname: Hökfelt
authors.affiliation: Department of Dermatology (R.L.) and Laura Bassi Centre of Expertise, Department of Pediatrics (B.K.), Paracelsus Private Medical University, Salzburg, Austria; The Florey Institute of Neuroscience and Mental Health, and Florey Department of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Victoria, Australia (A.L.G.); Schools of Physiology and Pharmacology and Clinical Sciences, Bristol University, Bristol, United Kingdom (F.E.H., S.A.H., D.W.); and Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden (T.H.) b.kofler@salk.at.
authors.forename: Barbara
authors.initials: B
authors.lastname: Kofler
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015195:Drug Design; D019004:Galanin / Q000235:genetics / Q000266:history / Q000378:metabolism*; D049673:History, 20th Century; D006801:Humans; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D058990:Molecular Targeted Therapy; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D044088:Receptors, Galanin / Q000187:drug effects* / Q000235:genetics / Q000266:history / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D044088:Receptors, Galanin; D019004:Galanin