EP2, but not EP4, steadily stimulates the Gαs-protein pathway
Fukushima, Keijo Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Senoo, Kanaho Tokushima University
Kurata, Naoki Tokushima University|Chiba University
Regan, John W. The University of Arizona
Fujino, Hiromichi Tokushima University Tokushima University Educator and Researcher Directory
black/Leff operational model calculation
prostanoid EP2 receptor
prostanoid EP4 receptor
EP2 and EP4 prostanoid receptors have long been considered to have similar roles, since they are known to couple with Gαs-protein and activate cAMP-mediated signaling pathways. In this study, we re-evaluated the results of cAMP assays with or without phosphodiesterase (PDE) inhibitor pretreatment. Here, we show that in the absence of PDE inhibitor pretreatment, prostaglandin E2 causes accumulation of cAMP in EP2 receptors, whereas markedly low levels of cAMP accumulated in EP4 receptors. By applying the Black/Leff operational model calculation, we found that EP2 receptors have a biased ability to intrinsically activate the Gαs-protein-mediated pathway, whereas EP4 receptors have strong biased activity for the Gαi-protein-mediated pathway. Thus, EP2 and EP4 receptors may not be similar Gαs-coupled receptors but instead substantially different receptors with distinct roles.
FEBS Open Bio
John Wiley & Sons|Federation of European Biochemical Societies
This is an open access article under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
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