Cloning and Characterization of Spliced Variants of the Porcine G Protein Coupled Receptor 120

Song, Tongxing; Peng, Jie; Ren, Jiao; Wei, Hong; Peng, Jian

doi:10.1155/2015/813816

Cited by 15 publications

(13 citation statements)

References 30 publications

(58 reference statements)

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“…As demonstrated in Table 1, ZQ-16 did not evoke calcium responses in HEK293 cells expressing other FFARs, including GPR40, GPR41, GPR119, and GPR120, at concentrations up to 100 mM. These receptors were functional, since they could be activated by reported ligands with EC 50 values comparable to published data (Briscoe et al, 2003;Xiong et al, 2004;Overton et al, 2006;Shimpukade et al, 2012;Hudson et al, 2013;Suzuki et al, 2013;Song et al, 2015). These results indicate that ZQ-16 is a selective agonist for GPR84.…”

Section: Resultssupporting

confidence: 73%

Discovery and Characterization of a Novel Small-Molecule Agonist for Medium-Chain Free Fatty Acid Receptor G Protein-Coupled Receptor 84

Zhang

Yang

et al. 2016

Journal of Pharmacology and Experimental Therapeutics

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G protein-coupled receptor 84 (GPR84) is a free fatty acid receptor activated by medium-chain free fatty acids with 9-14 carbons. It is expressed mainly in the immune-related tissues, such as spleen, bone marrow, and peripheral blood leukocytes. GPR84 plays significant roles in inflammatory processes and may represent a novel drug target for the treatment of immune-mediated diseases. However, the lack of potent and specific ligands for GPR84 hindered the study of its functions and the development of potential clinical applications. Here, we report the screen of 160,000 smallmolecule compounds with a calcium mobilization assay using a human embryonic kidney 293 cell line stably expressing GPR84 and Ga16, and the identification of 2-(hexylthio)pyrimidine-4,6-diol (ZQ-16) as a potent and selective agonist of GPR84 with a novel structure. ZQ-16 activates several GPR84-mediated signaling pathways, including calcium mobilization, inhibition of cAMP accumulation, phosphorylation of extracellular signal-regulated protein kinase 1/2, receptor desensitization and internalization, and receptor-b-arrestin interaction. This compound may be a useful tool to study the functions of GPR84 and a potential candidate for further structural optimization.

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Section: Resultssupporting

confidence: 73%

Discovery and Characterization of a Novel Small-Molecule Agonist for Medium-Chain Free Fatty Acid Receptor G Protein-Coupled Receptor 84

Zhang

Yang

et al. 2016

Journal of Pharmacology and Experimental Therapeutics

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“…3 and S8). Indeed, rat islet architecture and composition are highly similar to those of mouse islets [54], and the sequence identities of rat and mouse GPR120 are highly similar [21,55] . Indeed, rat islet architecture and composition are highly similar to those of mouse islets [54], and the sequence identities of rat and mouse GPR120 are highly similar [21,55] .…”

Section: Discussionmentioning

confidence: 94%

Insulinotropic effects of GPR120 agonists are altered in obese diabetic and obese non-diabetic states

Zhang

Wang

et al. 2017

Clinical Science

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G-protein-coupled receptor 120 (GPR120) is a putative target for obesity and diabetes therapies. However, it remains controversial whether resident GPR120 plays a direct regulatory role in islet β-cell insulin secretion. The present study examined this issue in isolated rodent islets and rat β-cell line INS-1E, and assessed the role of GPR120 in islet insulin secretion in obese non-diabetic (OND) and diabetic states. GPR120 expression was detected in rodent islet β-cells. Docosahexaenoic acid (DHA) and synthetic GPR120 agonist GSK137647 (GSK) augmented insulin release from rat/mouse islets and INS-1E; DHA effects were partially mediated by GPR40. GPR120 knockdown and overexpression attenuated and enhanced DHA effects in INS-1E respectively. DHA and GSK improved postprandial hyperglycaemia of diabetic mice. Inhibition of calcium signalling in INS-1E reduced GPR120 activation-induced insulinotropic effects. The insulinotropic effects of DHA/GSK were amplified in OND rat islets, but diminished in diabetic rat islets. GPR120 and peroxisome proliferator-activated receptor γ (PPARγ) expression were elevated in OND islets and palmitic acid (PA)-treated INS-1E, but reduced in diabetic islets and high glucose-treated INS-1E. PPARγ activation increased GPR120 expression in rat islets and INS-1E. DHA and GSK induced protein kinase B (Akt)/extracellular signal-regulated kinase (ERK) phosphorylation in rodent islets and INS-1E, and these effects were altered in OND and diabetic states. Taken together, the present study indicates that (i) GPR120 activation has an insulinotropic influence on β-cells with the involvement of calcium signalling; (ii) GPR120 expression in β-cells and GPR120-mediated insulinotropic effects are altered in OND and diabetic states in distinct ways, and these alterations may be mediated by PPARγ.

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“…Only a few published papers have reported FFAR4 expression in bovine tissues, namely adipose tissue [ 63 , 64 ]. In other species, FFAR4 is expressed in adipose tissue, spleen and intestine in pigs [ 65 ], while in human and rodents, its expression is more widely reported in additional tissues (immune cells, pancreatic cells, lung, muscle, liver and placenta) [ 42 , 66 – 69 ]. We demonstrated here that FFAR4 is localized in the vicinity of the cellular membrane in GCs, as expected for a G protein-coupled receptor.…”

Section: Discussionmentioning

confidence: 99%

Docosahexaenoic acid (DHA) effects on proliferation and steroidogenesis of bovine granulosa cells

Maillard

Desmarchais

Durcin

et al. 2018

Reprod Biol Endocrinol

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BackgroundDocosahexaenoic acid (DHA) is a n-3 polyunsaturated fatty acid (PUFA) belonging to a family of biologically active fatty acids (FA), which are known to have numerous health benefits. N-3 PUFAs affect reproduction in cattle, and notably directly affect follicular cells. In terms of reproduction in cattle, n-3 PUFA-enriched diets lead to increased follicle size or numbers.MethodsThe objective of the present study was to analyze the effects of DHA (1, 10, 20 and 50 μM) on proliferation and steroidogenesis (parametric and/or non parametric (permutational) ANOVA) of bovine granulosa cells in vitro and mechanisms of action through protein expression (Kruskal-Wallis) and signaling pathways (non parametric ANOVA) and to investigate whether DHA could exert part of its action through the free fatty acid receptor 4 (FFAR4).ResultsDHA (10 and 50 μM) increased granulosa cell proliferation and DHA 10 μM led to a corresponding increase in proliferating cell nuclear antigen (PCNA) expression level. DHA also increased progesterone secretion at 1, 20 and 50 μM, and estradiol secretion at 1, 10 and 20 μM. Consistent increases in protein levels were also reported for the steroidogenic enzymes, cytochrome P450 family 11 subfamily A member 1 (CYP11A1) and hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1 (HSD3B1), and of the cholesterol transporter steroidogenic acute regulatory protein (StAR), which are necessary for production of progesterone or androstenedione. FFAR4 was expressed in all cellular types of bovine ovarian follicles, and in granulosa cells it was localized close to the cellular membrane. TUG-891 treatment (1 and 50 μM), a FFAR4 agonist, increased granulosa cell proliferation and MAPK14 phosphorylation in a similar way to that observed with DHA treatment. However, TUG-891 treatment (1, 10 and 50 μM) showed no effect on progesterone or estradiol secretion.ConclusionsThese data show that DHA stimulated proliferation and steroidogenesis of bovine granulosa cells and led to MAPK14 phosphorylation. FFAR4 involvement in DHA effects requires further investigation, even if our data might suggest FFAR4 role in DHA effects on granulosa cell proliferation. Other mechanisms of DHA action should be investigated as the steroidogenic effects seemed to be independent of FFAR4 activation.Electronic supplementary materialThe online version of this article (10.1186/s12958-018-0357-7) contains supplementary material, which is available to authorized users.

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Cloning and Characterization of Spliced Variants of the Porcine G Protein Coupled Receptor 120

Cited by 15 publications

References 30 publications

Discovery and Characterization of a Novel Small-Molecule Agonist for Medium-Chain Free Fatty Acid Receptor G Protein-Coupled Receptor 84

Discovery and Characterization of a Novel Small-Molecule Agonist for Medium-Chain Free Fatty Acid Receptor G Protein-Coupled Receptor 84

Insulinotropic effects of GPR120 agonists are altered in obese diabetic and obese non-diabetic states

Docosahexaenoic acid (DHA) effects on proliferation and steroidogenesis of bovine granulosa cells

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