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FEBS Lett. 2013 Aug 2;587(15):2399-404. doi: 10.1016/j.febslet.2013.05.067. Epub 2013 Jun 13.

Succinate receptor GPR91, a Gα(i) coupled receptor that increases intracellular calcium concentrations through PLCβ.

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  • 1Discovery Sciences, AstraZeneca R&D, 43183 Mölndal, Sweden.


Succinate has been reported as the endogenous ligand for GPR91. In this study, succinate was confirmed to activate GPR91 resulting in both 3'-5'-cyclic adenosine monophosphate (cAMP) inhibition and inositol phosphate formation in a pertussis toxin (PTX)-sensitive manner. GPR91 agonist-mediated effects detected using dynamic mass redistribution (DMR) were inhibited with PTX, edelfosine and U73122 demonstrating the importance of not only the Gαi pathway but also PLCβ. These results show that GPR91 when expressed in HEK293s cells couples exclusively through the Gαi pathway and acts through Gαi not only to inhibit cAMP production but also to increase intracellular Ca(2+) in an inositol phosphate dependent mechanism via PLCβ activation.

Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.


3′–5′-cyclic adenosine monophosphate; BSA; DMR; ERK; FACS; FLIPR; GPCR; GPR91; GTPγS; HTRF; IP(1); MAPK; PLCβ; PTX; SUCNR1; Succinate; bovine serum albumin; cAMP; dynamic mass redistribution; extracellular-signal-regulated kinase; fluorescence-activated cell sorting; fluorescent imaging plate reader; guanosine 5′-[γ-(35)S]-triphosphate; homogeneous time resolved fluorescence; inositol-1-phosphate; mitogen-activated protein kinase; pertussis toxin; succinate receptor 1

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