Succinate GPCR Assays
Background of Succinate Receptors
The succinate receptor is the only subtype of the succinate G protein-coupled receptor family. It was first found in a megacaryocytic cell line in 1995, which was regarded as homology with the P2Y receptor. However, it was subsequently found that the ligand of the succinate receptor was not a purinergic ligand but a succinate. Similar to P2Y12, P2Y13, and P2Y14 receptors, succinate receptors almost exclusively couple to the Gi/Go family.
Fig.1 Crystal structure of a humanized (K18E, K269N) rat succinate receptor SUCNR1(GPR91). (Davenport, 2019)
Distributions and Functions of Succinate Receptors
The succinate receptors are distributed in the kidney, platelets, T cells, B cells, monocytes, and macrophages. It has been demonstrated that succinate receptors are activated by physiological levels of the Kreb's cycle intermediate succinate and other dicarboxylic acids like maleate. They participate in multiple pathological and physiological processes, including modulation of renin production, retinal angiogenesis, inflammation, and the immune response.
Subtypes and Mechanisms of Succinate Receptors
Succinate receptors are a family of G protein-coupled receptors activated by their endogenous ligand succinic acid. There is only one subtype of receptor, succinate receptor 1. The signal transduction is mediated by Gi/Go proteins and Gq/G11 proteins.
| Receptor | Gene | Mechanism | Agonists | Antagonists |
| Succinate receptor 1 | SUCNR1 |
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Assay List of Succinate Receptor
Creative Biolabs can provide a range of assays of the succinate receptor. You can choose the assay in the list or contact us for more information:
Published Data
| Paper Title | Identification and pharmacological characterization of succinate receptor agonists |
| Journal | British journal of pharmacology |
| Published | 2017 |
| Abstract | The succinate receptor (SUCNR1) is a metabolic sensor that is involved in metabolic homeostasis and may be important in multiple pathological and physiological processes. The study aimed to define the function of succinate receptors as there are no pharmacological tools available. They reported a family of potent synthetic agonists against SUCNR1. They screened a library of succinate analogues and analyzed their activity on SUCNR1. In addition, they established a model for a pharmacophore and a binding site for the succinate receptor. The results of those two assays indicated new agonists. Furthermore, various bioassays, including measurement of cAMP levels, [Ca2+]i mobilization, TGF-α shedding, and recruitment of arrestin 3. They also evaluated the in vivo effects of activating succinate receptors with these new agonists on rat BP. |
| Result |
The study has identified that cis-epoxysuccinic acid and cis-1,2-cyclopropanedicarboxylic acid were succinate receptor agonists, which have similar efficacy to that of succinic acid. The results showed that the cis-epoxysuccinic acid reduced cAMP levels was pEC50 = 5.57 ± 0.02 (EC50 = 2.7 μM), while succinate was pEC50 = 4.54 ± 0.08 (EC50 = 29 μM). Therefore, the results indicated that the cis-epoxysuccinic acid was 10- to 20-fold more potent than succinic acid on succinate receptors. The results of in vitro assays demonstrated the same potency of the three agonists. In addition, both cis-epoxysuccinic and cis-1,2-cyclopropanedicarboxylic acid were as potent as succinate in increasing rat BP.
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Fig.2 cis Conformation of the negative charges is an essential feature for succinate receptor agonists. (Geubelle, 2017)
References
- Davenport A. P.; et al. Succinate receptor (version 2019.3) in the IUPHAR/BPS Guide to Pharmacology Database. IUPHAR/BPS Guide to Pharmacology CITE. 2019, 2019(3).
- Geubelle, P.; et al. Identification and pharmacological characterization of succinate receptor agonists. British journal of pharmacology. 2017, 174(9): 796-808.
