The succinate receptor as a novel therapeutic target for oxidative and metabolic stress-related conditions.
The succinate receptor as a novel therapeutic target for oxidative and metabolic stress-related conditions.
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DOI：
10.3389/fendo.2012.00022
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发表时间：
2012
影响因子：
5.2
通讯作者：
Robben JH
中科院分区：
文献类型：
--
作者：
Ariza AC;Deen PM;Robben JH
琥珀酸受体（也称为GPR 91）是一种G蛋白偶联受体，与P2 Y嘌呤受体家族密切相关。它在多种组织中表达，包括血细胞、脂肪组织、肝脏、视网膜和肾脏。在这些组织中，这种受体和它的配体琥珀酸最近出现作为新的介质在局部应激的情况下，包括缺血，缺氧，毒性，和高血糖症。其中，琥珀酸受体参与免疫细胞向移植组织的募集。此外，它被证明在糖尿病视网膜病变的发展中起关键作用。然而，最重要的是，肾脏中局部增加的琥珀酸水平和琥珀酸受体激活的作用，刺激全身和局部的肾素-血管紧张素系统，开始显现：琥珀酸受体是高血压和糖尿病和代谢综合征中可能的纤维化发展的关键介质。这使得琥珀酸受体成为一个有希望的药物靶点，以抵消或预防这些扩展性疾病中的心血管和纤维化缺陷。最近开发的SUCNR 1特异性拮抗剂为这些疾病的模型研究开辟了新的可能性，并可能最终为患者的治疗提供新的机会。
The succinate receptor (also known as GPR91) is a G protein-coupled receptor that is closely related to the family of P2Y purinoreceptors. It is expressed in a variety of tissues, including blood cells, adipose tissue, the liver, retina, and kidney. In these tissues, this receptor and its ligand succinate have recently emerged as novel mediators in local stress situations, including ischemia, hypoxia, toxicity, and hyperglycemia. Amongst others, the succinate receptor is involved in recruitment of immune cells to transplanted tissues. Moreover, it was shown to play a key role in the development of diabetic retinopathy. However, most prominently, the role of locally increased succinate levels and succinate receptor activation in the kidney, stimulating the systemic and local renin–angiotensin system, starts to unfold: the succinate receptor is a key mediator in the development of hypertension and possibly fibrosis in diabetes mellitus and metabolic syndrome. This makes the succinate receptor a promising drug target to counteract or prevent cardiovascular and fibrotic defects in these expanding disorders. Recent development of SUCNR1-specific antagonists opens novel possibilities for research in models for these disorders and may eventually provide novel opportunities for the treatment of patients.