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• W2104259759 abstract "The GPRC6A receptor is a recently “deorphanized” class C G protein–coupled receptor. We and others have shown that this receptor is coactivated by basic l-<i>α</i>-amino acids and divalent cations, whereas other groups have also suggested osteocalcin and testosterone to be agonists. Likewise, the GPRC6A receptor has been suggested to couple to multiple G protein classes albeit via indirect methods. Thus, the exact ligand preferences and signaling pathways are yet to be elucidated. In the present study, we generated a Chinese hamster ovary (CHO) cell line that stably expresses mouse GPRC6A. In an effort to establish fully the signaling properties of the receptor, we tested representatives of four previously reported GPRC6A agonist classes for activity in the G_q, G_s, G_i, and extracellular-signal regulated kinase signaling pathways. Our results confirm that GPRC6A is activated by basic l-<i>α</i>-amino acids and divalent cations, and for the first time, we conclusively show that these responses are mediated through the G_q pathway. We were not able to confirm previously published data demonstrating G_i- and G_s-mediated signaling; neither could we detect agonistic activity of testosterone and osteocalcin. Generation of the stable CHO cell line with robust receptor responsiveness and optimization of the highly sensitive homogeneous time resolved fluorescence technology allow fast assessment of G_q activation without previous manipulations like cotransfection of mutated G proteins. This cell-based assay system for GPRC6A is thus useful in high-throughput screening for novel pharmacological tool compounds, which are necessary to unravel the physiologic function of the receptor." @default.
• W2104259759 created "2016-06-24" @default.
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• W2104259759 date "2013-09-05" @default.
• W2104259759 modified "2023-10-10" @default.
• W2104259759 title "Delineation of the GPRC6A Receptor Signaling Pathways Using a Mammalian Cell Line Stably Expressing the Receptor" @default.
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• W2104259759 doi "https://doi.org/10.1124/jpet.113.206276" @default.
• W2104259759 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24008333" @default.
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