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.
Footnotes
R.L. and A.L.G. contributed equally to this work.
Support to A.L.G. was provided by NHMRC (Australia) (Fellowship Grant 1005985), a NARSAD Independent Investigator Award, and the Victorian Government Operational Infrastructure Support Programme. Support to F.E.H., S.A.H., and D.W. was provided by the Medical Research Council, Wellcome Trust, and Diabetes UK. Support to T.H. was provided by The Marianne and Marcus Wallenberg Foundation, the Swedish Research Council, Funds from Karolinska Institutet, a NARSAD Distinguished Investigator Award, an unrestricted Bristol-Myers Squibb Neuroscience grant, and the 6th Framework Program of the European Union (NewMood, LSHM-CT-2004-503474). Support for this work was provided by a grant from the Austrian Research Promotion Agency (FFG, 822782/THERAPEP) to B.K.
- Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics
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