Third prize: Prostaglandin E(2)-3 receptor is involved in ureteral contractility in obstruction.
OBJECTIVE
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.


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.


CONCLUSIONS
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).
Ankem
Murali K
MK
Division of Urology, Department of Surgery, University of Wisconsin-Madison Medical School, Madison, Wisconsin 53792, USA.
Jerde
Travis J
TJ
Wilkinson
Eric R
ER
Nakada
Stephen Y
SY
D000818:Animals; D005260:Female; D009119:Muscle Contraction / Q000502:physiology*; D009130:Muscle, Smooth / Q000503:physiopathology*; D018078:Receptors, Prostaglandin E / Q000502:physiology*; D058308:Receptors, Prostaglandin E, EP3 Subtype; D013552:Swine; D014513:Ureter / Q000503:physiopathology; D014517:Ureteral Obstruction / Q000503:physiopathology*
D018078:Receptors, Prostaglandin E; D058308:Receptors, Prostaglandin E, EP3 Subtype