The differential functional coupling of phosphodiesterase 4 to human DP and EP2 prostanoid receptors stimulated with PGD2 or PGE2

Okura, Iori; Hasuoka, Nanae; Senoo, Kanaho; Suganami, Akiko; Fukushima, Keijo; Regan, John W.; Mashimo, Masato; Murayama, Toshihiko; Tsutsumi, Yutaka; Fujino, Hiromichi

doi:10.1007/s43440-021-00247-x

Cited by 2 publications

(1 citation statement)

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“…Of note, in HEK‐EP4 cells under the influence of IBMX, PGE 2 treatment led to the formation of approximately half of the potential E max level of cAMP in HEK‐EP2 cells, demonstrating EP4 receptor‐mediated adenylyl cyclase activity. However, without IBMX pretreatment, PGE 2 accumulated markedly low levels of practically formed cAMP, suggesting that PGE 2 ‐stimulated EP4 receptors exert greater effects on PDE activity, and/or PGE 2 ‐stimulated EP2 receptors do not activate PDE to the extent of EP4 receptors, as similarly discussed for D‐type prostanoid receptors and EP2 receptors [ 14 ].…”

Section: Resultsmentioning

confidence: 95%

The Gαs‐protein‐mediated pathway may be steadily stimulated by prostanoid EP2 receptors, but not by EP4 receptors

et al. 2022

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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.

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Section: Resultsmentioning

confidence: 95%