Galanin and galanin receptors.

Abstract

The development of a strain of galanin knockout mice has provided confirmation of a neuroendocrine role for galanin, as well as supporting results of previous physiological investigations indicating a role for galanin in analgesia and neuropathic pain, and potentially in neuronal growth and regeneration processes. Whether elevation of galanin expression in neurodegenerative disorders such as Alzheimer's disease represents a survival response or exacerbates functional deficit in afflicted individuals remains to be determined. More detailed analysis of the phenotype of the galanin knockout mouse should provide insights into the physiological role of galanin in memory and learning processes, as well as in hypothalamic function and other aspects of neuroendocrine regulation. Biochemical and molecular cloning efforts have demonstrated that the multiplicity of actions of galanin is matched by complexity in the distribution and regulation of galanin and its receptors. A focus on characterisation of galanin receptors has resulted in the molecular cloning of three receptor subtypes to date. The distribution and functional properties of these receptors have not yet been fully elucidated, currently precluding assignment of discrete functions of galanin to any one receptor subtype. It is not currently possible to reconcile available pharmacological data using analogs of galanin and chimeric peptides in functional assay systems with the pharmacological properties of cloned receptor subtypes. This highlights the value of further knockout approaches targeting galanin receptor subtypes, but also raises the possibility of the existence of additional receptor subtypes that have yet to be cloned, or that receptor activity may be modulated by regulatory molecules that remain to be identified. The development of receptor subtype-specific compounds remains a high priority to advance work in this area. The ability to selectively modulate the many different actions of galanin, through a clearer understanding of receptor structure-function relationships and neuronal distribution, promises to provide important insights into the molecular and cellular basis of galanin action in normal physiology, and may provide lead compounds with therapeutic application in the prevention and treatment of a range of disorders.