The Succinate Receptor as a Novel Therapeutic Target for Oxidative and Metabolic Stress-Related Conditions
Open accessAbstract
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.
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Previously, direct receptor-mediated anti-inflammatory effects of ACTH and succinate on immune cells associated with blockages of pro-inflammatory polarization have been shown.
“Previously, the direct receptor-mediated anti-inflammatory effects of ACTH and succinate on immune cells associated with blockages of pro-inflammatory polarization have been shown [51,52,89].”
From Protective Effects of PGC-1α Activators on Ischemic Stroke in a Rat Model of Photochemically Induced Thrombosis (2021) · cites this paper as [89]
The section “Tissue Distribution and (Patho)Physiological Roles of SUCNR1” describes receptor-mediated effects of succinate on dendritic cells, but says succinate potentiates inflammatory cytokine production rather than blocking pro-inflammatory activity. “Future Perspectives” likewise says SUCNR1 signaling may increase inflammation. These passages do not address ACTH. (LLM, conf=0.90)
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- Authors
- Ariza, A. C., Deen, P. M. T., & Robben, J. H.
- Affiliations
- Radboud University Nijmegen (NL)
- Corresponding author
- Robben, Joris Hubertus
- Venue
- Frontiers in Endocrinology
- Publisher
- Frontiers Media SA
- Published
- 2012
- Volume
- 3
- Pages
- 22-22
- ISSN
- 1664-2392 (ISSN-L)
- PMC
- PMC3355999
- OpenAlex
- W2138027442
- Cited by
- 211
- References
- 43
- Citations by year
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- FWCI
- 5.62
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc
- Locations
- Frontiers in Endocrinology (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Radboud Repository (Radboud University) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- Funders
- European Commission (201590)
- Nierstichting (KJPB 09.012)
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (865.07.002)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- succinate receptor, GPR91, SUCNR1, G protein-coupled receptors, succinic acid, metabolic stress, oxidative stress, hypertension, diabetic nephropathy, diabetic retinopathy, renin-angiotensin system, renal fibrosis, metabolic syndrome, diabetes mellitus, immune cell recruitment, therapeutic target
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