Galanin receptor signalling

The three galanin receptors, GAL₁, GAL₂ and GAL₃, share a number of characteristics as members of the 7-TM GPCR family, but their functional coupling and signal transduction pathways are substantially different, which contributes to the diversity of galanin-mediated effects, depending on the tissue/cell type and its particular G-protein repertoire (see [17] for review).

Distribution of galanin, galanin-like peptide and galanin receptors in brain and other tissues

The distribution of galanin mRNA and galanin-immunoreactivity has been mapped in adult rat and mouse brain and spinal cord and to differing degrees in several other species, including primate and human brain, and several non-mammalian vertebrates. Similarly, the distribution of GALP mRNA and GALP immunoreactivity was described in the rat and mouse brain [12,27]. The distribution of GALP mRNA-positive neurons has also been reported in macaque brain [4-5].

Subsequent to reports of the central distribution of [¹²⁵I]-galanin binding sites [24,33], the distribution of GAL₁, GAL₂ and GAL₃ mRNAs was reported in rat and mouse brain and spinal cord, using both in situ hybridization and RT-PCR (see [18] and [11] and references cited therein). Indeed, the central distributions of GAL₁, GAL₂ and GAL₃ mRNA were mapped soon after their cloning. In the mouse and rat, GAL₁ mRNA is widely expressed with high expression in olfactory structures and sub-regions/nuclei of the amygdala, thalamus, hypothalamus, pons, medulla and spinal cord [2,10,25-26]. GAL₂ mRNA is also broadly expressed in the CNS, with high levels present in the hippocampus, particularly in the dentate gyrus and the CA3 field, and in the supraoptic, arcuate and mammillary nuclei of the hypothalamus [2,9,26]. In the hindbrain, GAL₂ mRNA is abundant in the spinal trigeminal tract and the dorsal vagal complex [2,26]. Anatomical studies have also identified GAL₁ and GAL₂ mRNA in cells within the subventricular zone and the rostral migratory stream, regions associated with neurogenesis in the adult brain [21,31]. GAL₃ mRNA is abundant in peripheral tissues, but has a more restricted distribution in the CNS than GAL₁ and GAL₂ mRNA, being confined to discrete areas of the hypothalamus (paraventricular, ventromedial and dorsomedial nuclei) and forebrain areas (medial septum/diagonal band of Broca, bed nucleus of the stria terminalis, medial amygdaloid nucleus), midbrain (periaqueductal gray) and hindbrain (DR nucleus, LC and lateral parabrachial nucleus) [25]. The presence of GAL₁ and GAL₂ mRNA in the spinal cord, including data on labeled neuron types and regulation of expression has also been reported [1,15]. Various reports also exist of the presence of galanin mRNA and immunoreactivity and galanin receptor mRNA in a range of other tissues (see [17-18] for recent review).

Multiple functions of galanin and galanin receptors in brain and other tissues and systems under normal and pathophysiological conditions

Galanin and galanin receptors have been linked to the regulation of a range of functions including metabolic and osmotic homeostasis [3,8,16], reproduction [8,29], nociception [19], arousal/sleep [32,34] and cognition [14,23], and these functions have been subsequently linked to the actions of specific galanin receptors. For example, GAL1 has been linked strongly with the CNS and PNS and with modulatory actions on neurotransmission and anxiety, reward and nociception and associated co-morbid conditions [30]; whereas GAL₂ is more broadly expressed, and in the CNS is implicated in neurodevelopment [2], modulation of neurotransmission [21] and affective behaviors [13,20,35], neurite outgrowth in normal hippocampus [6], and neuronal survival and neurogenesis in injured hippocampus [6,21,28]. Galanin and galanin receptors have also been associated with regulation of neurogenesis and embryonic and adult neural stem cells, paracrine effects in bone [22] and more recent data also indicate an emerging role for galanin and galanin receptors in myelination [7], stroke-related damage, neurodegeneration, and alcohol and nicotine addiction, and in innate immunity, inflammation, diabetes and cancer (see [17] for review). Galanin-like peptide likely signals via a yet unidentified receptor, as it is fully active in galanin receptor deficient mice (see [17] for review).

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