The following is a summary of “PGE2 binding to EP2 promotes ureteral stone expulsion by relaxing ureter via the cAMP-PKA pathway,” published in the June 2024 issue of Urology by Su et al.
This study delves into the mechanisms underlying PGE2-induced relaxation of the ureter and its role in facilitating the expulsion of ureteral stones.
Using immunofluorescence and Western blot techniques, researchers precisely localized EP receptors within the ureter. In vitro experiments systematically evaluated the effects of PGE2, along with receptor agonists and antagonists, on the relaxation dynamics of ureteral smooth muscle. A ureteral stone model was constructed using flowable resin, and postoperative ureteral tissue from obstruction surgeries was analyzed via Western blot to assess the expression levels of EP receptors and the PGE2 terminal synthase mPGES-1. Furthermore, PGE2 was administered to smooth muscle cells to investigate its downstream effects on cAMP levels and PKA phosphorylation.
The findings confirmed significant expression of EP2 and EP4 proteins in ureteral smooth muscle, with EP2 predominantly localized on the cell membrane and EP4 within the nucleus, as observed through immunofluorescence. In vitro studies demonstrated that PGE2 induced dose-dependent relaxation of the ureter, achieving a maximum diastolic rate of 70.94 ± 4.57% at a concentration of 30 µM. Importantly, this effect was attenuated by EP2 antagonists but not by EP4 antagonists. Analysis of obstructed ureters revealed heightened expression of mPGES-1 and EP2 proteins (P < 0.01), underscoring their potential role in stone-related pathophysiology. Furthermore, PGE2 treatment of smooth muscle cells led to elevated levels of cAMP and phosphorylated PKA, indicative of activation of the cAMP-PKA pathway.
In conclusion, the study elucidates that PGE2 binding to EP2 receptors mediates ureteral relaxation via the cAMP-PKA signaling pathway. These findings provide a robust theoretical framework for exploring novel therapeutic strategies involving PGE2 in the management of ureteral stones. Future research endeavors could leverage this mechanistic understanding to optimize treatment approaches aimed at enhancing stone expulsion and alleviating ureteral obstruction.
Source: bmcurol.biomedcentral.com/articles/10.1186/s12894-024-01504-w
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