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 post-obstruction, 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 (G(alpha)i signaling-protein inhibitor [EP-3 blockade]) 500 ng/mL, a concentration- response curve (10(-9) M-10(-5) M) to PGE(2), PGF(2), sulprostone (EP 3 agonist), or 0.01% ethanol (vehicle) was created (N = 4). RESULTS: In the normal ureters, PGE(2) relaxed both pertussis toxin-treated and control tissues. In obstructed segments, PGE(2) 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(2) 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 PGE(2).
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 post-obstruction, 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 (G(alpha)i signaling-protein inhibitor [EP-3 blockade]) 500 ng/mL, a concentration- response curve (10(-9) M-10(-5) M) to PGE(2), PGF(2), sulprostone (EP 3 agonist), or 0.01% ethanol (vehicle) was created (N = 4). RESULTS: In the normal ureters, PGE(2) relaxed both pertussis toxin-treated and control tissues. In obstructed segments, PGE(2) 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(2) 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 PGE(2).
Authors: Matthias Oll; Claudia Baumann; Turang E Behbahani; Alexander von Ruecker; Stefan C Müller; Jörg Ellinger Journal: BMC Urol Date: 2012-12-10 Impact factor: 2.264