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.

中文翻译：

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甘丙肽和受体的生理学、信号传导和药理学：三个十年的新兴多样性。

30 年前，甘丙肽首次被确定为“经典神经肽”，其作用主要是作为大脑和周围神经系统中神经传递的调节剂。其他结构相关的肽——甘丙肽样肽和阿拉林——在脑和其他组织中具有不同的生物学作用，尽管与甘丙肽不同，它们的同源受体目前尚不清楚。在过去的二十年中，除了许多神经元作用外，还描述了甘丙肽和其他甘丙肽家族肽的许多非神经元作用。这些包括与神经干细胞、大脑中的非神经元细胞（如胶质细胞）、内分泌功能、对新陈代谢的影响、能量稳态和骨骼中的旁分泌作用相关的作用。大量新数据也表明甘丙肽在先天免疫中的新兴作用，炎症和癌症。甘丙肽已被证明通过与三种 G 蛋白偶联受体 GAL1、GAL2 和 GAL3 相互作用以及通过多种转导途径发出信号，包括抑制 cAMP/PKA (GAL1、GAL3) 和刺激磷脂酶 C (GAL2)。在这篇综述中，我们强调了新型甘丙肽受体特异性激动剂和拮抗剂的重要性。此外，其他方法，包括新的转基因小鼠品系（例如最近表征的 GAL3 敲除小鼠），结合基于病毒的技术，代表了更好地评估甘丙肽系统生理学所需的关键工具。这些反过来将有助于确定甘丙肽/甘丙肽受体系统在多种人类疾病中的潜在目标，包括疼痛、情绪障碍、癫痫、