PGE2 promotes ureteral stone expulsion through ureteral relaxation via EP2 receptor

Abstract

Abstract This study aimed to assess the relaxant impact of PGE2 on the ureter and whether it becomes a facilitator of calculi expulsion following calculi formation. We identified the presence of EP receptors in the ureter using Western blot and immunofluorescence techniques. In vitro experiments were conducted to assess the impact of PGE2, receptor antagonists, and agonists on the rate of ureteral relaxation. Ureteral calculi models were constructed to gather ureteral tissue from the postoperative side of the obstruction. Western blot analysis was used to assess protein expression levels of EP receptors and the PGE2 terminal synthase mPGES-1. Western blot analysis revealed the presence of EP2 and EP4 protein expression in ureteral smooth muscle. Immunofluorescence revealed predominant localization of EP2 on the cell membrane and EP4 in the nucleus. In vitro experiments demonstrated that PGE2 induced concentration-dependent relaxation of the ureter. EP2 antagonists effectively inhibited the relaxation effect, while EP4 antagonists had no such inhibitory effect. In the presence of ureteral stones, the ureters on the obstructed side can become a favorable factor for stone expulsion by upregulating EP2 expression, enhancing PGE2 synthesis, and promoting ureteral relaxation via cAMP. In conclusion, PGE2 binding to EP2 induces ureteral relaxation, and in the context of ureteral calculi, it serves as a facilitator for stone expulsion.