The Succinate Receptor as a Novel Therapeutic Target for Oxidative and Metabolic Stress-Related Conditions
Open Access
- 1 January 2012
- journal article
- Published by Frontiers Media SA in Frontiers in Endocrinology
- Vol. 3, 22
- https://doi.org/10.3389/fendo.2012.00022
Abstract
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.Keywords
This publication has 40 references indexed in Scilit:
- Discovery of a potent and selective small molecule hGPR91 antagonistBioorganic & Medicinal Chemistry Letters, 2011
- Expression and Iron-Dependent Regulation of Succinate Receptor GPR91 in Retinal Pigment EpitheliumInvestigative Ophthalmology & Visual Science, 2011
- Succinate modulates Ca2+ transient and cardiomyocyte viability through PKA-dependent pathwayCell Calcium, 2010
- The role of the GPR91 ligand succinate in hematopoiesisJournal of Leukocyte Biology, 2009
- Succinate is a paracrine signal for liver damageJournal of Hepatology, 2007
- Gene Expression Profiles During Hepatic Stellate Cell Activation in Culture and In VivoGastroenterology, 2007
- Resident dendritic cells are the predominant TNF-secreting cell in early renal ischemia–reperfusion injuryKidney International, 2007
- Nonezymatic formation of succinate in mitochondria under oxidative stressFree Radical Biology & Medicine, 2006
- The Pathobiology of Diabetic ComplicationsDiabetes, 2005
- Tricarboxylic acid cycle intermediate pool size and estimated cycle flux in human muscle during exerciseAmerican Journal of Physiology-Endocrinology and Metabolism, 1998