Galanin and Galanin Receptors

Iismaa, Tiina P.; Shine, John

doi:10.1007/978-3-540-49421-8_12

Cited by 92 publications

(51 citation statements)

References 186 publications

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“…The Nterminal sequence of this 29 amino acid neuropeptide (30 amino acids in humans) is highly conserved across species (reviewed in Ho È kfelt et al, 1991;Bartfai et al, 1992;Crawley, 1995). More recently three galanin receptors have been cloned (reviewed in Iismaa and Shine, 1999;Branchek et al, 2000). Immunocytochemical localization of galanin in the mammalian brain demonstrated a widespread distribution in the rodent peripheral and central nervous systems, with high concentrations of galanin in hypothalamic nuclei, ventral forebrain, amygdala, hippocampus, brainstem and spinal cord (reviewed in Ho È kfelt et al, 1991Ho È kfelt et al, , 1998Merchenthaler et al, 1993;Pe Â rez et al, 2001;Counts et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

“…Galanin inhibits the evoked release of acetylcholine and glutamate in rat hippocampal slices and in vivo microdialysate (Fisone et al, 1987;O È gren et al, 1996;Robinson et al, 1996). Galanin attenuates the activation of adenylate cyclase and phosphatidyl inositol hydrolysis in rat hippocampus and cortex (reviewed in Karelson and Langel, 1998;Iismaa and Shine, 1999).…”

Section: Introductionmentioning

confidence: 99%

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Galanin overexpressing transgenic mice

et al. 2002

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Summary Galanin overexpressing transgenic mice (GAL-tg) were generated on two different promoters. Both lines of GAL-tg displayed high levels of galanin in the hippocampus and reduced sensitivity to seizures, as compared to their respective wildtype littermate controls (WT). Performance deficits on learning and memory tasks, impaired long-term potentiation, reduced hippocampal excitability, lower evoked glutamate release, and reduced numbers of choline acetyltransferase immunoreactive neurons in the horizontal limb of the diagonal band were detected in GAL-tg as compared to WT. Changes in sensitivity to nociceptive stimuli were demonstrated in one line. GAL-tg represent a new model for investigating the biological actions of endogenous galanin, and for testing novel therapeutics based on galanin receptor ligands. ß

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Galanin overexpressing transgenic mice

et al. 2002

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“…There are three galanin receptors, GALR1-GALR3, which all belong to the family of seven transmembrane-spanning, G protein-coupled receptors (26)(27)(28)(29). They are found in many areas of the rat brain, as first shown with autoradiographic ligand-binding methodology (30,31), and later with in situ hybridization (ISH)/quantitative real-time PCR (qPCR) (32)(33)(34)(35)(36).…”

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confidence: 99%

Depression-like behavior in rat: Involvement of galanin receptor subtype 1 in the ventral periaqueductal gray

Wang

Barde

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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The neuropeptide galanin coexists in rat brain with serotonin in the dorsal raphe nucleus and with noradrenaline in the locus coeruleus (LC), and it has been suggested to be involved in depression. We studied rats exposed to chronic mild stress (CMS), a rodent model of depression. As expected, these rats showed several endophenotypes relevant to depression-like behavior compared with controls. All these endophenotypes were normalized after administration of a selective serotonin reuptake inhibitor. The transcripts for galanin and two of its receptors, galanin receptor 1 (GALR1) and GALR2, were analyzed with quantitative real-time PCR using laser capture microdissection in the following brain regions: the hippocampal formation, LC, and ventral periaqueductal gray (vPAG). Only Galr1 mRNA levels were significantly increased, and only in the latter region. After knocking down Galr1 in the vPAG with an siRNA technique, all parameters of the depressive behavioral phenotype were similar to controls. Thus, the depression-like behavior in rats exposed to CMS is likely related to an elevated expression of Galr1 in the vPAG, suggesting that a GALR1 antagonist could have antidepressant effects.dorsal raphe | neuropeptide | siRNA | stress | transmitter coexistence T he indoleamine hypothesis of depression was formulated some five decades ago (1, 2), in parallel with the catecholamine hypothesis (3, 4), and has been supported by the success of selective serotonin reuptake inhibitors (SSRIs) for treatment of major depression (MD) (5). However, in a considerable number of cases, SSRIs are associated with side effects or lack of efficacy. For example, after treatment with SSRIs, only one-third of patients obtain full remission of symptoms (6). Therefore, there is an ongoing search for new medications targeting mood disorders, such as MD and anxiety. Here, neuropeptides and their receptors, the most diverse family of neurotransmitters in the brain (7), have been extensively explored (5,(8)(9)(10)(11)(12)(13)(14)(15)(16)(17), including galanin and its three receptors.Galanin is a 29-aa (30-aa in humans) neuropeptide (18) with a wide distribution in the rat brain (19,20), where it is coexpressed with noradrenaline/norepinephrine (NA) in locus coeruleus (LC) neurons and with 5-hydroxytryptamine (5-HT) in dorsal raphe nucleus (DR) neurons (21-25). There are three galanin receptors, GALR1-GALR3, which all belong to the family of seven transmembrane-spanning, G protein-coupled receptors (26-29). They are found in many areas of the rat brain, as first shown with autoradiographic ligand-binding methodology (30, 31), and later with in situ hybridization (ISH)/quantitative real-time PCR (qPCR) (32-36). The galanin system has been associated with numerous physiological and pathophysiological functions (29), including depression-and anxiety-like behaviors.There is early evidence from studies on the rat that central administration of galanin influences mood-related behavior in a region-specific way (37, 38), and also that galanin is prodepres...

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“…In the locus coeruleus and dorsal raphe of rats galanin reduces firing rate and induces hyperpolarization with a marked desensitization (4-7). So far, three receptor subtypes, galanin R receptor (GALR) 1, GALR2, and GALR3, have been identified, all belonging to the G proteincoupled receptor (GPCR) superfamily (8)(9)(10). GALR1 is distributed mainly in the CNS, including the noradrenergic locus coeruleus neurons (11), where it may mediate the hyperpolarizing effect of galanin (12).…”

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confidence: 99%

“…The widespread distribution of GALR2 suggests that it is involved in numerous physiological events, including prolactin release, lactation, growth hormone release, feeding, emotion, memory, nociception, cellular growth, nerve regeneration, pancreatic islet function, cardiovascular tone, peripheral metabolism, and reproduction (9). It has been shown that activation of GALR2 leads to accumulation of inositol phosphate, mobilization of intracellular Ca 2ϩ , and activation of a Ca 2ϩ -dependent Cl Ϫ channel via G q/11 -type G proteins (14,17,20,21).…”

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confidence: 99%

Visualization of a functionally enhanced GFP-tagged galanin R2 receptor in PC12 cells: Constitutive and ligand-induced internalization

Sheng

Kjær

Zheng

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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Trafficking of the galanin R2 receptor (GALR2) fused with enhanced GFP (EGFP) was studied by using confocal fluorescence microscopy. The fusion protein was predominantly localized on the plasma membrane with some intracellular fluorescent structures (vesicles), mainly in the perinuclear region. Incubation with galanin resulted in a concentration-dependent increase in intracellular Ca 2؉ concentration levels, suggesting that the GALR2-EGFP conjugate is functional. After blocking endocytosis with methyl-␤-cyclodextrin GALR2-EGFP expression was increased on the surface and decreased in the cytoplasm. Blocking endocytic recycling with monensin caused an increase of intracellular GALR2-EGFP accumulation and a decrease of fluorescence on the plasma membrane. GALR2-EGFP on the plasma membrane was internalized within 5-10 min after treatment with galanin or AR-M1896, a selective GALR2 agonist, with a dramatic reduction in plasma membrane localization and appearance in intracellular vesicles. Neither M35 nor M40, two galanin analogues with putative antagonistic action, prevented GALR2 agonist-induced internalization of GALR2-EGFP, suggesting that they are not antagonists at this receptor under the present circumstances. Galanin stimulation at low temperature caused GALR2-EGFP aggregation and clustering on the surface but no translocation to cytoplasm. After coincubation with galanin the GALR2-EGFP was colocalized with internalized Texas red-transferrin, a marker of the clathrin endocytic pathway. Hyperosmotic sucrose inhibited internalization of GALR2-EGFP. Taken together these findings indicate that GALR2 undergoes constitutive endocytosis and recycling and that both ligand-independent and liganddependent internalization use the clathrin-dependent endocytic recycling pathway.

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Galanin and Galanin Receptors

Cited by 92 publications

References 186 publications

Galanin overexpressing transgenic mice

Galanin overexpressing transgenic mice

Depression-like behavior in rat: Involvement of galanin receptor subtype 1 in the ventral periaqueductal gray

Visualization of a functionally enhanced GFP-tagged galanin R2 receptor in PC12 cells: Constitutive and ligand-induced internalization

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