Expression Cloning of a Rat Hypothalamic Galanin Receptor Coupled to Phosphoinositide Turnover

Smith, Kip; Forray, Carlos; Walker, Mary W.; Jones, Kenneth A.; Tamm, Joseph A.; Bard, Jonathan; Branchek, Theresa A.; Linemeyer, David L.; Gerald, Christophe

doi:10.1074/jbc.272.39.24612

Cited by 189 publications

(211 citation statements)

References 37 publications

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“…Among these receptors, GalR1 and GalR3 mainly activate G i/o types of G proteins mediating inhibitory actions of galanin (Habert-Ortoli et al, 1994;Burgevin et al, 1995;Parker et al, 1995;see Branchek et al, 2000). In contrast, the GalR2 subtype can transmit either stimulatory effects of galanin, for example, on neurotransmitter release, acting via G q/11 types of G proteins (Smith et al, 1997;Wang et al, 1997;Fathi et al, 1998), or it can inhibit neurotransmission via G i/o types (Fathi et al, 1998;Wang et al, 1998;see Branchek et al, 2000). Thus, the physiological effects of galanin are varied and complex.…”

Section: Introductionmentioning

confidence: 99%

Differential Role of Galanin Receptors in the Regulation of Depression-Like Behavior and Monoamine/Stress-Related Genes at the Cell Body Level

Kuteeva

Wardi

Lundström

et al. 2008

Neuropsychopharmacol

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The present study on rat examined the role of galanin receptor subtypes in regulation of depression-like behavior as well as potential molecular mechanisms involved in the locus coeruleus (LC) and dorsal raphe (DR). The effect of intracerebroventricular (i.c.v.) infusion of galanin or galanin receptor GalR1-and GalR2-selective ligands was studied in the forced swim test, followed by quantitative in situ hybridization studies. Naive control, non-treated (swim control), saline-and fluoxetine-treated rats were used as controls in the behavioral and in situ hybridization studies. Subchronic treatment with fluoxetine reduced immobility and climbing time. Intracerebroventricular infusion of galanin, the GalR1 agonist M617 or the GalR2 antagonist M871 increased, while the GalR2(R3) agonist AR-M1896 decreased, immobility time compared to the aCSF-treated animals. Galanin also decreased the time of climbing. Galanin mRNA levels were upregulated by the combination of injection + swim stress in the saline-and the fluoxetine-treated groups in the LC, but not in the DR. Also tyrosine hydroxylase levels in the LC were increased following injection + swim stress in the saline-and fluoxetine-treated rats. Tryptophan hydroxylase 2 and serotonin transporter mRNAs were not significantly affected by any treatment. 5-HT 1A mRNA levels were downregulated following i.c.v. galanin, M617 or AR-M1896 infusion. These results indicate a differential role of galanin receptor subtypes in depression-like behavior in rodents: GalR1 subtype may mediate 'prodepressive' and GalR2 'antidepressant' effects of galanin. Galanin has a role in behavioral adaptation to stressful events involving changes of molecules important for noradrenaline and/or serotonin transmission.

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Section: Introductionmentioning

confidence: 99%

Differential Role of Galanin Receptors in the Regulation of Depression-Like Behavior and Monoamine/Stress-Related Genes at the Cell Body Level

Kuteeva

Wardi

Lundström

et al. 2008

Neuropsychopharmacol

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“…Three subtypes of galanin receptors have been cloned, GalR1 (Habert-Ortoli et al 1994;Burgevin et al 1995;Parker et al 1995) GalR2 (Howard et al 1997;Smith et al 1997;Wang et al 1997a) and GalR3 (Wang et al 1997b;Smith et al 1998), which all belong to the superfamily of G-protein-linked receptors. The autoradiographic receptor binding studies have indicated moderate galanin R1 and R2 receptor binding in the DRN .…”

Section: Discussionmentioning

confidence: 99%

Galanin Is a Potent In Vivo Modulator of Mesencephalic Serotonergic Neurotransmission

Kehr

Yoshitake

Wang

et al. 2002

Neuropsychopharmacology

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“…GALR2 is more widely distributed in peripheral tissues and to a lesser extent in the central nervous system (Wang and Gustafson, 1998). Most authors describe the receptor's ability to activate phospholipase C-b in a pertussis toxin-insensitive manner, representing indirect evidence for coupling to G q proteins (Pang et al, 1998;Smith et al, 1997;. GALR3 is prominently expressed in spleen, heart and testis as well as in several regions of Figure 7 Stimulation of GALR2 causes the reorganization of the actin cytoskeleton in Swiss 3T3 ®broblasts.…”

Section: Discussionmentioning

confidence: 99%

“…While most authors agree on the receptor's ability to couple to phospholipase C-b isoforms via G q/11 proteins, the additional interaction of GALR2 with G i or G o is discussed controversially (Pang et al, 1998;Smith et al, 1997;Wang et al, 1997a. The galanin-induced inhibition of isoproterenoldependent cAMP accumulation in HEK293 cells coexpressing the human b 2 AR and GALR2 is considerably smaller than the e ect of carbachol acting on the M 2 muscarinic receptor.…”

Section: Discussionmentioning

confidence: 99%

The galanin receptor type 2 initiates multiple signaling pathways in small cell lung cancer cells by coupling to Gq, Gi and G12 proteins

et al. 2000

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Neuropeptides like galanin produced and released by small cell lung cancer (SCLC) cells are considered principal mitogens in these tumors. We identi®ed the galanin receptor type 2 (GALR2) as the only galanin receptor expressed in H69 and H510 cells. Photoa nity labeling of G proteins in H69 cell membranes revealed that GALR2 activates G proteins of three subfamilies: G q , G i , and G 12 . In H69 cells, galanin-induced Ca 2+ mobilization was pertussis toxin-insensitive. While phorbol ester-induced extracellular signal-regulated kinase (ERK) activation required protein kinase C (PKC) activity, preincubation of H69 cells with the PKCinhibitor GF109203X had no e ect on galanin-dependent ERK activity. A rise of the intracellular calcium concentration was necessary and su cient to mediate galanin-induced ERK activation. In support of G i coupling, stimulation of GALR2 expressed in HEK293 cells inhibited isoproterenol-induced cAMP accumulation and raised cAMP levels in COS-7 cells when coexpressed with a chimeric Ga S -Ga i protein. In H69 cells, galanin activated the monomeric GTPase RhoA and induced stress ®ber formation in Swiss 3T3 cells expressing GALR2. Thus, we provide the ®rst direct evidence that in SCLC the mitogenic neuropeptide galanin, interacting with GALR2, simultaneously activates multiple classes of G proteins and signals through the G q phospholipase C/calcium sequence and a G 12 /Rho pathway. Oncogene (2000) 19, 4199 ± 4209.

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Expression Cloning of a Rat Hypothalamic Galanin Receptor Coupled to Phosphoinositide Turnover

Cited by 189 publications

References 37 publications

Differential Role of Galanin Receptors in the Regulation of Depression-Like Behavior and Monoamine/Stress-Related Genes at the Cell Body Level

Differential Role of Galanin Receptors in the Regulation of Depression-Like Behavior and Monoamine/Stress-Related Genes at the Cell Body Level

Galanin Is a Potent In Vivo Modulator of Mesencephalic Serotonergic Neurotransmission

The galanin receptor type 2 initiates multiple signaling pathways in small cell lung cancer cells by coupling to Gq, Gi and G12 proteins

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