Galanin receptor subtypes and ligand binding

Florén, Anders; Land, Tiit; Langel, Ülo

doi:10.1054/npep.2000.0808

Cited by 84 publications

(51 citation statements)

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“…GAL binds to at least three receptors termed galanin receptor (GALR) 1, GALR2 and GALR3, which have been cloned and characterized in rat, mouse and human (Branchek et al, 2000;Floren et al, 2000;Counts et al, 2003). All GALRs are membrane-bound, G proteincoupled receptors, but they differ with respect to their amino acid sequence, distribution, G protein coupling and the cellular signaling mechanism (Branchek et al, 2000;Floren et al, 2000;Counts et al, 2003).…”

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confidence: 99%

“…All GALRs are membrane-bound, G proteincoupled receptors, but they differ with respect to their amino acid sequence, distribution, G protein coupling and the cellular signaling mechanism (Branchek et al, 2000;Floren et al, 2000;Counts et al, 2003). In general, GALR1 and GALR3 are strongly coupled to the inhibition of adenylyl cyclase, whereas GALR2 stimulates phospholipase C and inositol phosphate production or is weakly coupled to adenylyl cyclase inhibition (Smith et al, 1997Wang et al, 1998).…”

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confidence: 99%

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Ectopic galanin expression and normal galanin receptor 2 and galanin receptor 3 mRNA levels in the forebrain of galanin transgenic mice

Counts

Pérez

et al. 2005

Neuroscience

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Abstract-The functional interactions of the neuropeptide galanin (GAL) occur through its binding to three G proteincoupled receptor subtypes: galanin receptor (GALR) 1, GALR2 and GALR3. Previously, we demonstrated that GALR1 mRNA expression was increased in the CA1 region of the hippocampus and discrete hypothalamic nuclei in galanin transgenic (GAL-tg) mice. This observation suggested a compensatory adjustment in cognate receptors in the face of chronic GAL exposure. To evaluate the molecular alterations to GALR2 and GALR3 in the forebrain of GAL overexpressing mice, we performed complementary quantitative, real-time PCR (qPCR), in situ hybridization, and immunohistochemistry in select forebrain regions of GAL-tg mice to characterize the neuronal distribution and magnitude of GAL mRNA and peptide expression and the consequences of genetically manipulating the neuropeptide GAL on the expression of GALR2 and GALR3 receptors. We found that GAL-tg mice displayed dramatic increases in GAL mRNA and peptide in the frontal cortex, posterior cortex, hippocampus, septal diagonal band complex, amygdala, piriform cortex, and olfactory bulb. Moreover, there was evidence for ectopic neuronal GAL expression in forebrain limbic regions that mediate cognitive and affective behaviors, including the piriform and entorhinal cortex and amygdala. Interestingly, regional qPCR analysis failed to reveal any changes in GALR2 or GALR3 expression in the GAL-tg mice, suggesting that, contrary to GALR1, these receptor genes are not under ligand-mediated regulatory control. The GAL-tg mouse model may provide a useful tool for the investigation of GAL ligand-receptor relationships and their role in normal cognitive and affective functions as well as in the onset of neurological disease.

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Ectopic galanin expression and normal galanin receptor 2 and galanin receptor 3 mRNA levels in the forebrain of galanin transgenic mice

Counts

Pérez

et al. 2005

Neuroscience

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“…In mammals, acute injection of galanin or active fragments such as galanin (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16), into the PVN, lateral and ventromedial hypothalamic nuclei, and the central nucleus of the amygdala, significantly increases food intake and produces rapid increases in the feeding response and total caloric intake [4,5,11,12] . The effects of galanin on feeding be-…”

Section: Effects Of Galanin On Food Intake and Energy Expenditurementioning

confidence: 99%

“…Galanin, a 29-amino-acid neuropeptide, is mainly distributed in central and peripheral nervous systems [6] . Currently, it is known that the galanin receptor subtypes include GalR1, GalR2 and GalR3, all of which are G protein-coupled receptors [7] and are distributed in the hypothalamus, amygdala, hippocampus, thalamus, brainstem, spinal cord and dorsal root ganglia [7][8][9] . Both GalR1 and GalR3 act through the Gi/o receptor, inhibiting adenyl cyclase and causing a decrease of cAMP [7,9] .…”

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confidence: 99%

Central nervous system regulation of food intake and energy expenditure: role of galanin-mediated feeding behavior

Fang

et al. 2011

Neurosci. Bull.

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Abstract:Galanin is a neuropeptide widely expressed in the brain. It is implicated in energy expenditure, feeding, and the regulation of body weight. Numerous studies have revealed that galanin regulates food intake via galanin receptors, 5-HT 1A receptor and adrenergic α-2 receptor. In this review, we summarize recent findings that reveal the essential role of galanin in increasing food intake as well as body weight and that identify the individual galanin receptor subtypes involved in the brain's modulation of food intake and energy expenditure, to provide a theoretical basis for further studies of different aspects of galanin action.

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“…These amino acids are located in the N-terminal helical part of galanin that it is made up of the same 15 aa in all species from which it was isolated (15,16). Fragments of galanin have shown low binding affinity but these peptides are vulnerable to the action of the peptidases and unable to cross the blood-brain barrier (17,18). Two nonpeptide antagonists of the galanin receptor have been reported, spirocoumaranon (Sch202596) (19) and 2,3-dihydro-2-(4-methylphenyl)-1,4-dithiepin-1,1,4,4-tetroxide (20) (see Fig.…”

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Synthesis of galmic: A nonpeptide galanin receptor agonist

Ceide

Trembleau²,

Haberhauer³

et al. 2004

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

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Galanin is a neuropeptide with a wide variety of biological functions. Few nonpeptide ligands, capable of activating galanin receptors, are available today. Based on known pharmacophores of galanin and the tripeptidomimetic galnon, a combinatorial library was formulated, synthesized, and screened against the galanin receptor. An active compound, galmic, was identified and tested in vitro and in vivo for its affinity and efficacy at galanin receptors. The present work describes the total synthesis of galmic, the synthesis of its oxazole precursors, the coupling of the building blocks into a linear trimer, and the macrolactamization reaction.galnon ͉ mimetic G alanin is a 29-aa-long (30 aa in humans) neuroendocrine peptide, whose physiological functions are regulated by G protein-coupled receptors. Galanin is found throughout the central and peripheral nervous systems and the gastrointestinal tract (1-4). The effects of this peptide include inhibition of insulin release (5-7), inhibition of neurotransmiters involved in regulation and memory acquisition (8), modulation of food intake (9, 10) and sexual behavior (11), as well as effects on controlling pain threshold (12, 13) and in the pathogenesis of Alzheimer's disease (14).Studies involving L-Ala-substituted analogues of galanin have identified Trp-2, Asn-5, and Tyr-9 as well as the N-terminal amino group as being critical determinants for receptor binding. These amino acids are located in the N-terminal helical part of galanin that it is made up of the same 15 aa in all species from which it was isolated (15, 16). Fragments of galanin have shown low binding affinity but these peptides are vulnerable to the action of the peptidases and unable to cross the blood-brain barrier (17,18). Two nonpeptide antagonists of the galanin receptor have been reported, spirocoumaranon (Sch202596) (19) and 2,3-dihydro-2-(4-methylphenyl)-1,4-dithiepin-1,1,4,4-tetroxide (20) (see Fig. 1), but there is only one nonpeptide galanin receptor ligand, galnon, that shows agonist activity (21).In this study, we report an example of a nonpeptide subtype selective agonist for the galanin receptor, galmic, discovered by application of a combinatorial library approach (22). MethodsExperimental. Reactions were performed under an argon atmosphere, NMR spectra were recorded on a Bruker DRX 600 spectrometer (unless otherwise mentioned), and the chemical shifts are given in ppm relative to tetramethylsilane. The spectra were referenced to deuterated solvents indicated in brackets in the analytical data. High-resolution MALDI-Fourier transform MS (FTMS) measurements were performed on an IonSPec (Lake Forest, CA) FTMS mass spectrometer by using 2,5-dihydroxybenzoic acid as the matrix. For TLC, silica plates IB2-F (J. T. Baker) were used. For column chromatography, silica gel 60, 230-400 mesh (Merck) was used. Preparative chromatographic plates and silica gel 60 F 254 (20 ϫ 20 cm, 0.5 mm) were used. Anhydrous solvents and chemicals were used as purchased from commercial suppliers. General Procedures. ...

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Galanin receptor subtypes and ligand binding

Cited by 84 publications

References 53 publications

Ectopic galanin expression and normal galanin receptor 2 and galanin receptor 3 mRNA levels in the forebrain of galanin transgenic mice

Ectopic galanin expression and normal galanin receptor 2 and galanin receptor 3 mRNA levels in the forebrain of galanin transgenic mice

Central nervous system regulation of food intake and energy expenditure: role of galanin-mediated feeding behavior

Synthesis of galmic: A nonpeptide galanin receptor agonist

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