Last update 01 Nov 2024

GALR2

Last update 01 Nov 2024

Basic Info

Synonyms

GAL2-R, galanin receptor 2, Galanin receptor type 2

+ [3]

Introduction

Receptor for the hormone galanin and GALP. Receptor for the hormone spexin-1 (PubMed:24517231). The activity of this receptor is mediated by G proteins that activate the phospholipase C/protein kinase C pathway (via G(q)) and that inhibit adenylyl cyclase (via G(i)).

Drugs associated with GALR2

NS-200

Target

GALR2

Mechanism

GALR2 agonists

Active Org.

Neuracle Science Co., Ltd.Startup [+1]

Originator Org.

Neuracle Science Co., Ltd.Startup

Active Indication

Neurogenic Bowel [+2]

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

WO2024132147

Patent Mining

Target

GALR2

Mechanism

GALR2 agonists

Active Org.

Lifearc

Originator Org.

Lifearc

Active Indication

Neurologic Manifestations

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

CN116751261

Patent Mining

Target

GALR2

Mechanism

GALR2 agonists

Active Org.

Zonsen Peplib Biotech Co., Ltd.Startup

Originator Org.

Zonsen Peplib Biotech Co., Ltd.Startup

Active Indication

Depression

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with GALR2

100 Translational Medicine associated with GALR2

0 Patents (Medical) associated with GALR2

357

Literatures (Medical) associated with GALR2

01 Dec 2024·General and Comparative Endocrinology

Differential activation of six galanin receptors by the spexin peptide in yellowtail kingfish (Seriola lalandi)

Article

Author: Cui, Aijun ; Xu, Yongjiang ; Jiang, Yan ; Tian, Zhenfang ; Huang, Hai ; Yu, Zhihua ; Wang, Bin

Spexin (SPX1) is a novel neuropeptide composed of 14 amino acids and well conserved across vertebrates, and it has been implicated in various physiological functions via galanin receptor 2 (GALR2) and GALR3. However, the detailed signaling pathways mediating its actions in target cells are still largely unknown. Accordingly, we addressed this issue in the present study using yellowtail kingfish as a model. SPX1 significantly increased CRE-luc activity in COS-7 cells expressing its cognate receptors GALR2a and GALR2b, and this stimulatory effect was attenuated by two inhibitors of the PKA pathway. Similarly, an evident induction of SRE-luc activity was observed when COS-7 cells transfected with GALR1b, GALR2a, GALR2b, GALR type 1, or GALR type 2 were challenged with SPX1, and two blockers of the PKC pathway suppressed this stimulatory action. Moreover, SPX1 markedly elevated NFAT-RE-luc activity in COS-7 cells expressing GALR1a, GALR2a, or GALR2b, and this promotion was inhibited by two antagonists of the Ca²⁺ route. Overall, our results have revealed that activation of six yellowtail kingfish galanin receptors by the SPX1 peptide may occur with different downstream signaling events, which could account for its pleotropic functions.

09 Jul 2024·Circulation

Spexin Diminishes Atrial Fibrillation Vulnerability by Acting on Galanin Receptor 2

Article

Author: Lu, Yanjie ; Zhang, Zhi-Ren ; Pan, Zhenwei ; Liu, Yang ; Zhang, Lingmin ; Li, Yue ; Shen, Kewei ; Yin, Dechun ; Yang, Jiming ; Li, Desheng ; Yang, Baofeng ; Li, Jialiang ; Gao, Kangyi ; Xuan, Lina ; Zhang, Yang ; Pei, Yao ; Zhou, Zhiwen ; Zhao, Lexin ; Song, Jiahui ; Bao, Hairong ; Li, Chenhong ; Li, Changzhu ; Zhao, Xinbo ; Xue, Genlong

BACKGROUND:G protein–coupled receptors play a critical role in atrial fibrillation (AF). Spexin is a novel ligand of galanin receptors (GALRs). In this study, we investigated the regulation of spexin and GALRs on AF and the underlying mechanisms.METHODS: Global spexin knockout (SPX-KO) and cardiomyocyte-specific GALRs knockout (GALR-cKO) mice underwent burst pacing electrical stimulation. Optical mapping was used to determine atrial conduction velocity and action potential duration. Atrial myocyte action potential duration and inward rectifying K + current ( IK1 ) were recorded using whole-cell patch clamps. Isolated cardiomyocytes were stained with Fluo-3/AM dye, and intracellular Ca 2+ handling was examined by CCD camera. A mouse model of AF was established by Ang-II (angiotensin II) infusion. RESULTS: Spexin plasma levels in patients with AF were lower than those in subjects without AF, and knockout of spexin increased AF susceptibility in mice. In the atrium of SPX-KO mice, potassium inwardly rectifying channel subfamily J member 2 ( KCNJ2 ) and sarcolipin ( SLN ) were upregulated; meanwhile, IK1 current was increased and Ca 2+ handling was impaired in isolated atrial myocytes of SPX-KO mice. GALR2-cKO mice, but not GALR1-cKO and GALR3-cKO mice, had a higher incidence of AF, which was associated with higher IK1 current and intracellular Ca 2+ overload. The phosphorylation level of CREB (cyclic AMP responsive element binding protein 1) was upregulated in atrial tissues of SPX-KO and GALR2-cKO mice. Chromatin immunoprecipitation confirmed the recruitment of p-CREB to the proximal promoter regions of KCNJ2 and SLN . Finally, spexin treatment suppressed CREB signaling, decreased IK1 current and decreased intracellular Ca 2+ overload, which thus reduced the inducibility of AF in Ang-II–infused mice. CONCLUSIONS: Spexin reduces atrial fibrillation susceptibility by inhibiting CREB phosphorylation and thus downregulating KCNJ2 and SLN transcription by GALR2 receptor. The spexin/GALR2/CREB signaling pathway represents a novel therapeutic avenue in the development of agents against atrial fibrillation.

15 Apr 2024·The FASEB Journal

Long‐term enhancements in antidepressant efficacy and neurogenesis: Effects of intranasal co‐administration of neuropeptide Y 1 receptor (NPY1R) and galanin receptor 2 (GALR2) agonists in the ventral hippocampus

Article

Author: Narváez, Manuel ; Fuxe, Kjell ; Borroto-Escuela, Dasiel O ; García-Casares, Natalia ; Hernández-García, Aracelis ; Barbancho-Fernández, Miguel Angel ; Beltran-Casanueva, Rasiel ; Sánchez-Pérez, Jose Andrés ; Serrano-Castro, Pedro Jesús

AbstractThis study evaluates the sustained antidepressant‐like effects and neurogenic potential of a 3‐day intranasal co‐administration regimen of galanin receptor 2 (GALR2) agonist M1145 and neuropeptide Y Y1 receptor (NPY1R) agonist [Leu31, Pro34]NPY in the ventral hippocampus of adult rats, with outcomes analyzed 3 weeks post‐treatment. Utilizing the forced swimming test (FST), we found that this co‐administration significantly enhances antidepressant‐like behaviors, an effect neutralized by the GALR2 antagonist M871, highlighting the synergistic potential of these neuropeptides in modulating mood‐related behaviors. In situ proximity ligation assay (PLA) indicated a significant increase in GALR2/NPYY1R heteroreceptor complexes in the ventral hippocampal dentate gyrus, suggesting a molecular basis for the behavioral outcomes observed. Moreover, proliferating cell nuclear antigen (PCNA) immunolabeling revealed increased cell proliferation in the subgranular zone of the dentate gyrus, specifically in neuroblasts as evidenced by co‐labeling with doublecortin (DCX), without affecting quiescent neural progenitors or astrocytes. The study also noted a significant uptick in the number of DCX‐positive cells and alterations in dendritic morphology in the ventral hippocampus, indicative of enhanced neuronal differentiation and maturation. These morphological changes highlight the potential of these agonists to facilitate the functional integration of new neurons into existing neural circuits. By demonstrating the long‐lasting effects of a brief, 3‐day intranasal administration of GALR2 and NPY1R agonists, our findings contribute significantly to the understanding of neuropeptide‐mediated neuroplasticity and herald novel therapeutic strategies for the treatment of depression and related mood disorders, emphasizing the therapeutic promise of targeting neurogenesis and neuronal maturation processes.

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GALR2

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