更新于：2024-11-01

GALR2

更新于：2024-11-01

基本信息

别名

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

+ [3]

简介

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)).

关联

项与 GALR2 相关的药物

NS-200

靶点

GALR2

作用机制

GALR2 agonists

在研机构

Neuracle Science Co., Ltd.初创企业 [+1]

原研机构

Neuracle Science Co., Ltd.初创企业

在研适应症

神经源性肠 [+2]

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

WO2024132147

专利挖掘

靶点

GALR2

作用机制

GALR2 agonists

在研机构

Lifearc

原研机构

Lifearc

在研适应症

神经系统表现

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

CN116751261

专利挖掘

靶点

GALR2

作用机制

GALR2 agonists

在研机构

湖南中晟全肽生化有限公司初创企业

原研机构

湖南中晟全肽生化有限公司初创企业

在研适应症

抑郁

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 GALR2 相关的临床结果

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100 项与 GALR2 相关的转化医学

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0 项与 GALR2 相关的专利（医药）

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357

项与 GALR2 相关的文献（医药）

2024-12-01·General and Comparative Endocrinology

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

Article

作者: 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.

2024-07-09·Circulation

Spexin Diminishes Atrial Fibrillation Vulnerability by Acting on Galanin Receptor 2

Article

作者: 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.

2024-04-15·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

作者: 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.

项与 GALR2 相关的新闻（医药）

2024-05-14

·生物探索

Circulation | 哈尔滨医科大学潘振伟/杨宝峰/张志仁/李悦发现心房颤动的潜在治疗新靶点

引言G蛋白偶联受体在心房颤动(AF)中起关键作用。Spexin是一种新型的丙氨酸受体( GALRs)配体。2024年5月10日，哈尔滨医科大学潘振伟、杨宝峰、张志仁及李悦共同通讯在Circulation（IF=38）在线发表题为“Spexin Diminishes Atrial Fibrillation Vulnerability by Acting on Galanin Receptor 2”的研究论文，该研究证明，Spexin通过作用于丙氨酸受体2减少心房颤动易感性。该研究表明，房颤患者的Spexin血浆水平低于非房颤患者，敲除Spexin会增加小鼠的房颤易感性。SPX-KO小鼠心房钾内整流通道亚家族J成员2 (KCNJ2)和肌磷脂(SLN)上调；同时，SPX-KO小鼠离体心房肌细胞I K1电流升高，Ca2+处理受损。GALR2-cKO小鼠，而不是GALR1-cKO和GALR3-cKO小鼠，具有更高的AF发生率，这与更高的IK1电流和细胞内Ca2+过载有关。SPX-KO和GALR2-cKO小鼠心房组织中环AMP反应元件结合蛋白1 (CREB)磷酸化水平上调。染色质免疫沉淀证实了p-CREB在KCNJ2和SLN的近端启动子区域的募集。最后，spexin处理抑制CREB信号，降低IK1电流和细胞内Ca2+过载，从而降低了 Ang-II注入小鼠AF的诱导性。总之，Spexin通过抑制CREB磷酸化，从而下调GALR2受体对KCNJ2和SLN的转录，从而降低房颤易感性。spexin/GALR2/CREB信号通路为房颤药物的开发提供了一条新的治疗途径。房颤(AF)是最常见的心律失常，具有相当高的发病率和死亡率，其治疗伴有不良的心房重构。目前治疗房颤的药理学策略疗效有限，且存在一定的不良反应。发现与房颤病理生理机制相关的新靶点可能会开辟新的治疗途径。房颤的进展是心房电和结构重构、自主神经失衡、Ca2+处理改变、代谢异常和遗传因素的结果。电重构导致心房有效不应期(AERP)和动作电位持续时间(APD)缩短，并导致APD适应性的丧失，这涉及到伴随的离子活性改变慢性房颤患者的离子通道重塑包括L型Ca2+电流(ICa, L)密度降低，向内整流K+电流(I K1)振幅增加和细胞内Ca2+处理紊乱。心脏SERCA2a(肌浆网Ca2+-ATP酶2a)参与Ca2+进入肌浆网的再摄取，并关键地决定了肌浆网(CaSR)中的钙含量和心脏的兴奋-收缩偶联。PLN(磷蛋白)和SLN(肌磷脂)是心脏SERCA泵活性的关键调节因子。细胞内Ca2+处理的变化降低了心房肌细胞的收缩功能，缩短了心房肌细胞的动作电位，诱发房颤。心房IK1密度的增加和细胞内Ca2+处理的紊乱在APD缩短和房颤的发生中起着关键作用。抑制心房IK1电流和恢复细胞内Ca2+处理具有开发房颤新药的潜力。模式图（Credit: Circulation）Spexin，也被称为神经肽Q，是最近发现的一种由14个氨基酸组成的肽激素。它广泛产生于大脑，包括下丘脑，以及周围组织，如胃肠道、肺、胰腺、肾脏、肾上腺和脂肪组织。Spexin也被分泌到血液可以改变器官和组织的生理功能。研究表明，肥胖儿童的spexin循环水平低于体重正常的同龄人此外，spexin是运动改善肥胖诱导的胰岛素抵抗和2型糖尿病的潜在介质。它涉及体内平衡功能，如代谢、能量稳态和生殖等。为了发挥这些作用，spexin结合到膜甘丙肽受体2 (GALR2)和甘丙肽受体3 (GALR3)，但不结合到甘丙肽受体1 (GALR1)。在之前的研究中，spexin可以保护心肌细胞免受缺氧诱导的代谢和线粒体功能障碍。该研究系统检测了spexin对AF易感性的影响及其分子机制。研究证明spexin通过GALR2/CREB(环AMP响应元件结合蛋白1)途径抑制Kir2.1和SLN的表达，从而减轻AF的易感性。Spexin/GALR2/CREB信号轴通过调控KCNJ2和SLN转录影响心房电重构和细胞内钙稳态，从而参与房颤的发病。Spexin治疗可抑制心房颤动的易感性，可能是一种治疗心房颤动的新药物。原文链接https://doi.org/10.1161/CIRCULATIONAHA.123.067517责编|探索君排版|探索君文章来源|“iNature”End往期精选围观一文读透细胞死亡(Cell Death) | 24年Cell重磅综述（长文收藏版）热文Nature | 破除传统：为何我们需要重新思考肿瘤的命名方式热文Nature | 2024年值得关注的七项技术热文Nature | 自身免疫性疾病能被治愈吗？科学家们终于看到了希望热文CRISPR技术进化史 | 24年Cell综述

临床结果

2023-02-06

·生物谷

甘丙素受体3−--治疗视网膜变性的新药理靶点

甘丙肽受体(GALRs)属于蛋白偶联受体(GPCRs)家族，包括GALR1、GALR2和GALR3三个亚型。GALR广泛分布于神经系统，但也在非神经组织中表达。甘丙肽受体(GALRs)属于蛋白偶联受体(GPCRs)家族，包括GALR1、GALR2和GALR3三个亚型。GALR广泛分布于神经系统，但也在非神经组织中表达。这些受体具有很高的序列同源性和结构相似性。然而，它们的组织分布模式和它们传递信号的G蛋白类型不同。重要的是，GALR3介导的信号在许多人类疾病的发病机制中起着核心作用，包括癫痫、酒精中毒、神经病理性疼痛、糖尿病和癌症，炎症反应的激活是这些疾病的主要标志。神经肽甘丙素受体3(GALR3)是一类A、G蛋白偶联受体，广泛表达于包括视网膜在内的神经系统。GALR3参与免疫和炎症反应的调节。严格控制这些过程对于维持视网膜内的动态平衡至关重要，也是维持视力所必需的。图片来源: https://doi.org/10.1016/j.phrs.2023.106675 近日，来自凯斯西储大学的研究者们在Pharmacological Research杂志上发表了题为“Galanin receptor 3-A new pharmacological target in retina degeneration”的文章，这项工作为评估GALR3作为开发抗视网膜变性新疗法的潜在靶点提供了药理学知识基础。在本研究中，研究者研究了GALR3在强光和视紫红质(Rho)基因P23H突变引发的视网膜病理中的作用，这些突变与氧化应激和炎症反应的激活有关。研究者使用药物抑制GALR3及其拮抗剂SNAP-37889和GALR3基因缺失的多阶段方法来调节GALR3信号。研究者在对全反式视网膜毒性敏感的视网膜色素上皮源性细胞(ARPE19)进行的体外实验表明，GALR3可能参与了细胞对这种光毒产物的应激反应。事实上，阻断ABCA4-/-/Rdh8-/-和野生型Balb/CJ小鼠的GALR3信号，对强光诱导的视网膜损伤敏感，保护了这些暴露在光下的小鼠的视网膜健康。与对照组相比，这些小鼠模型的视网膜形态和功能得到了显著改善，应激反应过程减少。此外，在P23H Rho基因敲入的小鼠视网膜色素变性(RP)模型中，GALR3的药物抑制和基因消融都延长了光感受器的存活。这些结果表明，GALR3信号在急性光诱导和慢性RP相关视网膜病变中起作用。缺乏Galr3可以保护视网膜免受光诱导的退化图片来源: https://doi.org/10.1016/j.phrs.2023.106675 综上所述，基于这项工作的结果，研究者首次证明GALR3在急性和慢性视网膜病变的病理发生中发挥关键作用。因此，GALR3作为治疗视网膜退行性疾病的靶点的潜力值得进一步研究。（生物谷 Bioon.com）参考文献 Joseph T. Ortega et al. Galanin receptor 3 - A new pharmacological target in retina degeneration. Pharmacol Res. 2023 Jan 21; 188:106675. doi: 10.1016/j.phrs.2023.106675. 内容来源于网络，如有侵权，请联系删除。