Background and Purpose: We previously found that prostaglandin (PG) E2 contracts acutely obstructed ureters while relaxing normal ureters. This study investigated the procontractile effects of the PG EP3 receptor in PGE 2-mediated contractility in obstructed and normal porcine ureters. Materials and Methods: We created unilateral ureteral obstruction laparoscopically using titanium clips in farm pigs; the contralateral ureters were dissected as sham controls. Ureters were harvested 48 hours postobstruction, cut into 5-mm segments, and suspended in water-jacketed tissue baths in Krebs buffer. Tissues were equilibrated for 1 hour, and spontaneous contractile rates were recorded. After 2 hours of incubation in Krebs (controls) or pertussis toxin (Gαi signaling-protein inhibitor [EP-3 blockade]) 500 ng/mL, a concentration-response curve (10-9 M-10 -5 M) to PGE2, PGF2α, sulprostone (EP 3 agonist), or 0.01% ethanol (vehicle) was created (N = 4). Results: In the normal ureters, PGE2 relaxed both pertussis toxin-treated and control tissues. In obstructed segments, PGE2 increased contractions by 60%; this was reversed by pertussis toxin to a 67% reduction in contractile rate. In both obstructed and contralateral segments, sulprostone induced contractility in the controls; this was attenuated by pertussis toxin. The PGF 2α produced a contractile effect in both the controls and the pertussis toxin-treated segments, demonstrating the selectivity of pertussis toxin for EP3 receptors. Conclusion: Our data indicate that the EP3 receptor is involved in hypercontractility during ureteral obstruction. However, it may not be the sole factor behind the condition-dependent effect of PGE2.
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