Delineation of the GPR15 receptor-mediated Gα protein signalling profile in recombinant mammalian cells

Autor: Yufang Deng, Ee Von Moo, Claudia Victoria Pérez Almería, Patrick R. Gentry, Line Vedel, Jesper M. Mathiesen, Hans Bräuner‐Osborne
Přispěvatelé: AIMMS, Medicinal chemistry
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Basic and Clinical Pharmacology and Toxicology, 131(2), 104-113. Wiley-Blackwell
Deng, Y, Moo, E V, Pérez Almería, C V, Gentry, P R, Vedel, L, Mathiesen, J M & Bräuner-Osborne, H 2022, ' Delineation of the GPR15 receptor-mediated Gα protein signalling profile in recombinant mammalian cells ', Basic and Clinical Pharmacology and Toxicology, vol. 131, no. 2, pp. 104-113 . https://doi.org/10.1111/bcpt.13738
Deng, Y, Moo, E V, Almería, C V P, Gentry, P R, Vedel, L, Mathiesen, J M & Bräuner-Osborne, H 2022, ' Delineation of the GPR15 receptor-mediated Gα protein signalling profile in recombinant mammalian cells ', Basic and Clinical Pharmacology and Toxicology, vol. 131, no. 2, pp. 104-113 . https://doi.org/10.1111/bcpt.13738
ISSN: 1742-7835
DOI: 10.1111/bcpt.13738
Popis: The GPR15 receptor is a G protein-coupled receptor (GPCR), which is activated by an endogenous peptide GPR15L(25–81) and a C-terminal peptide fragment GPR15L(71–81). GPR15 signals through the Gi/o pathway to decrease intracellular cyclic adenosine 3′,5′-monophosphate (cAMP). However, the activation profiles of the GPR15 receptor within Gi/o subtypes have not been examined. Moreover, whether the receptor can also couple to Gs, Gq/11 and G12/13 is unclear. Here, GPR15L(25–81) and GPR15L(71–81) are used as pharmacological tool compounds to delineate the GPR15 receptor-mediated Gα protein signalling using a G protein activation assay and second messenger assay conducted on living cells. The results show that the GPR15 receptor preferentially couples to Gi/o rather than other pathways in both assays. Within the Gi/o family, the GPR15 receptor activates all the subtypes (Gi1, Gi2, Gi3, GoA, GoB and Gz). The Emax and activation rates of Gi1, Gi2, Gi3, GoA and GoB are similar, whilst the Emax of Gz is smaller and the activation rate is significantly slower. The potencies of both peptides toward each Gi/o subtype have been determined. Furthermore, the GPR15 receptor signals through Gi/o to inhibit cAMP accumulation, which could be blocked by the application of the Gi/o inhibitor pertussis toxin.
Databáze: OpenAIRE
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