α-Ketoglutarate GPCR Assays
Background of α-Ketoglutarate Receptors
α-Ketoglutarate (α-KG) is a glutamine catabolism product and a citric acid cycle intermediary. It's also a natural ligand for 2-oxoglutarate receptor 1 (OXGR1). OXGR1 is a member of the class A family of seven transmembranes G protein-coupled receptors. Recent studies showed that OXGR1 has also been described as a receptor for both α-ketoglutarate and cysteinyl leukotriene. OXGR1 acts as the novel regulator of pathological hypertrophy so that has served as the therapeutic target for pathological cardiac hypertrophy.
Fig.1. Schematic diagram of possible signaling pathway regulated by OXGR1 in the heart. (Omede, 2016)
Distributions and Functions of α-Ketoglutarate Receptors
The expression of OXGR1 mRNA can be detected in various tissues, such as the kidney, placenta, and fetal brain. What’s more, the expression of OXGR1 in the heart can act as an α-ketoglutarate receptor to regulate cardiac hypertrophy. However, its precise function in cardiac pathophysiology remains to be studied. OXGR1 can be activated by LTE4 to mediate various allergic and hypersensitivity responses in cells.
Mechanisms of α-Ketoglutarate Receptors
| Receptor | Gene | Mechanism | Agonists | Antagonists |
| Oxoglutarate receptor 1 | OXGR1 |
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Assay List of α-Ketoglutarate Receptor
Creative Biolabs can provide a range of assays of α-ketoglutarate receptor. You can choose the assay in the list or contact us for more information:
| Assay No. | Assay Name | Host Cell | Assay Type | Datasheet |
|---|---|---|---|---|
| Calcium Flux Assay | ||||
| S01YF-1122-KX967 | Magic™ Human OXGR1 In Vitro Calcium Flux Assay | CHO-K1 | Calcium Flux Assay | |
Published Data
| Paper Title | α-Ketoglutarate Upregulates Collecting Duct (Pro)renin Receptor Expression, Tubular Angiotensin II Formation, and Na+ Reabsorption During High Glucose Conditions |
| Journal | Frontiers in cardiovascular medicine |
| Published | 2021 |
| Abstract | Diabetes mellitus (DM) typically results in elevated levels of glucose (HG) in plasma and urine. The (pro)renin receptor (PRR) is a key regulator of renal Na+ handling. PRR was found to be expressed in intercalating (IC) cells of the collecting duct and bound to renin to promote angiotensin (Ang) II formation and ultimately Na+ reabsorption. The researchers believe that HG leads to αKG secretion and OXGR1 activation, thereby increasing PRR expression in CD cells. Ultimately, this effect promotes intraductal AngII formation and Na+ reabsorption. We used streptozotocin (STZ)-induced diabetic mice treated with the OXGR1 antagonist montelukast (ML) and ultimately found higher urinary αKG and PRR expression as well as increased urinary AngII levels and Na+ retention. |
| Result |
In this paper, we performed experiments using mice with STZ-induced hyperglycemia. Finally, these mice were found to have increased urinary αKG and increased expression of PRR in the medullary collecting duct as well as increased urinary AngII levels and Na+ retention. We also found that pharmacological blockade of the αKG receptor OXGR1 with ML in vivo and in vitro prevented the upregulation of PRRs in medullary collecting duct cells under HG conditions. Furthermore, attenuated upregulation of PRR by ML was accompanied by attenuated urinary AngII excretion and increased urinary sodium excretion. Finally, our data also suggested that metabolic pathways may be involved in the regulation of intracellular RAS components.
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Fig.2. Working hypothesis representing the effects of high glucose on the activation of the tricarboxylic acid (TCA) cycle and accumulation of αKG leading to OXGR1 activation. (Guerrero, 2022)
References
- Omede, A.; et al. The oxoglutarate receptor 1 (OXGR1) modulates pressure overload-induced cardiac hypertrophy in mice. Biochemical and biophysical research communications. 2016, 479(4): 708-714.
- Guerrero, A.; et al. α-Ketoglutarate Upregulates Collecting Duct (Pro) renin Receptor Expression, Tubular Angiotensin II Formation, and Na+ Reabsorption During High Glucose Conditions. Frontiers in cardiovascular medicine. 2021, 8: 415.
