Forskolin-free cAMP assay for Gi-coupled receptors

Gilissen, Julie; Geubelle, Pierre; Dupuis, Nadine; Laschet, Céline; Pirotte, Bernard; Hanson, Julien

doi:10.1016/j.bcp.2015.09.010

Cited by 40 publications

(65 citation statements)

References 47 publications

(66 reference statements)

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“…Several authors repeatedly confirmed G i activation by demonstrating a decrease of cAMP levels upon succinate binding to SUCNR1 (Fig. 3), in both heterologous and native systems (Gilissen et al, 2015;Gnana-Prakasam et al, 2011 ;Hakak et al, 2009;Hogberg et al, 2011 ;Sundström et al, 2013). However, the view of SUCNR1 being coupled to G q has been challenged and it was proposed by several authors that the observed [Ca 2+ ] i mobilization was a consequence of PLC-β activation by the βγ dimer (Fig.…”

Section: Succinate Receptor 1 Signaling Pathwaysmentioning

confidence: 78%

“…Only maleate and methylmalonate were able to induce a response with 5-to 10-fold lower potency compared to succinate (He et al, 2004). The partial agonist nature of maleate on SUCNR1 was independently confirmed recently (Gilissen et al, 2015).…”

Section: Ligandsmentioning

confidence: 80%

“…Hogberg et al also showed desensitization of SUCNR1 in platelets (Hogberg et al, 2011). The coupling of activated receptor to arrestins 2 and 3 is very weak (Gilissen et al, 2015;Southern et al, 2013). Therefore, it is likely that homologous desensitization and internalization occur by a mechanism that does not involve arrestins.…”

Section: Succinate Receptor 1 Signaling Pathwaysmentioning

confidence: 97%

“…However, the view of SUCNR1 being coupled to G q has been challenged and it was proposed by several authors that the observed [Ca 2+ ] i mobilization was a consequence of PLC-β activation by the βγ dimer (Fig. 3) (Gilissen et al, 2015;Sundström et al, 2013). The discrepancy between results may reflect distinct G protein partners among different cell types or artifacts induced by overexpression of the receptor.…”

Section: Succinate Receptor 1 Signaling Pathwaysmentioning

confidence: 99%

“…3). Some results indicate that ERK activation is G i -dependent and should probably be mediated through the dimer βγ (Gilissen et al, 2015;Hakak et al, 2009). SUCNR1 is internalized into vesicular structures upon succinate exposure in HEK293 cells (He et al, 2004).…”

Section: Succinate Receptor 1 Signaling Pathwaysmentioning

confidence: 99%

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Insight into SUCNR1 (GPR91) structure and function

Gilissen

Jouret

Pirotte

et al. 2016

Pharmacology & Therapeutics

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101

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SUCNR1 (or GPR91) belongs to the family of G protein-coupled receptors (GPCR), which represents the largest group of membrane proteins in human genome. The majority of marketed drugs targets GPCRs, directly or indirectly. SUCNR1 has been classified as an orphan receptor until a landmark study paired it with succinate, a citric acid cycle intermediate.According to the current paradigm, succinate triggers SUCNR1 signaling pathways to indicate local stress that may affect cellular metabolism. SUCNR1 implication has been well documented in renin-induced hypertension, ischemia/reperfusion injury, inflammation and immune response, platelet aggregation and retinal angiogenesis. In addition, the SUCNR1-induced increase of blood pressure may contribute to diabetic nephropathy or cardiac hypertrophy.The understanding of SUCNR1 activation, signaling pathways and functions remains largely elusive, which calls for deeper investigations. SUCNR1 shows a high potential as an innovative drug target and is probably an important regulator of basic physiology. In order to achieve the full characterization of this receptor, more specific pharmacological tools such as small-molecules modulators will represent an important asset. In this review, we describe the structural features of SUCNR1, its current ligands and putative binding pocket. We give an exhaustive overview of the known and hypothetical signaling partners of the receptor in different in vitro and in vivo systems. The link between SUCNR1 intracellular pathways and its pathophysiological roles are also extensively discussed.

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Section: Succinate Receptor 1 Signaling Pathwaysmentioning

confidence: 78%

Section: Ligandsmentioning

confidence: 80%

Section: Succinate Receptor 1 Signaling Pathwaysmentioning

confidence: 97%

Section: Succinate Receptor 1 Signaling Pathwaysmentioning

confidence: 99%

Section: Succinate Receptor 1 Signaling Pathwaysmentioning

confidence: 99%

See 3 more Smart Citations

Insight into SUCNR1 (GPR91) structure and function

Gilissen

Jouret

Pirotte

et al. 2016

Pharmacology & Therapeutics

Self Cite

101

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Microbial metabolite succinate activates solitary chemosensory cells in the human sinonasal epithelium

Sell

Tan

Lin

et al. 2023

Int Forum Allergy Rhinol

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Background Succinate, although most famous for its role in the Krebs cycle, can be released extracellularly as a signal of cellular distress, particularly in situations of metabolic stress and inflammation. Solitary chemosensory cells (SCCs) express SUCNR1, the succinate receptor, and modulate type 2 inflammatory responses in helminth and protozoal infections in the small intestine. SCCs are the dominant epithelial source of interleukin‐25, as well as an important source of cysteinyl leukotrienes in the airway, and have been implicated as upstream agents in type 2 inflammation in chronic rhinosinusitis (CRS) and asthma. Methods In this study, we used scRNAseq analysis, live cell imaging of intracellular calcium from primary sinonasal air‐liquid interface (ALI) cultures from 1 donor, and measure antimicrobial peptide release from 5 donors to demonstrate preliminary evidence suggesting that succinate can act as a stimulant of SCCs in the human sinonasal epithelium. Results Results from scRNAseq analysis show that approximately 10% of the SCC/ionocyte cluster of cells expressed SUCNR1 as well as a small population of immune cells. Using live cell imaging of intracellular calcium, we also demonstrate that clusters of cells on primary sinonasal ALI cultures initiated calcium‐mediated signaling in response to succinate stimulation. Furthermore, we present evidence that primary sinonasal ALI cultures treated with succinate had increased levels of apical beta‐defensin 2, an antimicrobial peptide, compared to treatment with a control solution. Conclusion Overall, these findings demonstrate the need for further investigation into the activation of the sinonasal epithelium by succinate in the pathogenesis of CRS.

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