TY  - EJOU
AU  - Klausner, Adam P. 
AU  - Johnson, Corey M. 
AU  - Stike, Aaron B. 
AU  - Speich, John E. 
AU  - Sabarwal, Vikram 
AU  - Miner, Amy S. 
AU  - Cleary, MaryEllen 
AU  - Koo, Harry P. 
AU  - Ratz, Paul H. 

TI  - Prostaglandin E<sub>2</sub> mediates spontaneous rhythmic contraction in rabbit detrusor muscle
T2  - Canadian Journal of Urology

PY  - 2011
VL  - 18
IS  - 2
SN  - 1488-5581

AB  - <b>Introduction:</b> The purpose of this investigation was to determine whether prostaglandin E2 (PGE2) is produced by rabbit detrusor muscle that is free of urothelium, and to demonstrate that PGE2 is responsible for the generation of spontaneous rhythmic contractions (SRC).<br/>

<b>Materials and Methods:</b> A bioassay was conducted in which the contraction frequency of rabbit detrusor strips was compared before and after the addition of superfusate obtained from incubated sections of rabbit detrusor. Specificity of the response was assessed using SC-51089, a PGE2 (EP1) receptor antagonist. The effects on tension development were also tested in artery segments treated with increasing doses of PGE2, PGF2α, and TXA2; femoral artery segments served as a negative control. Production of PGE2 was confirmed using enzyme immunoassay (EIA) kits.<br/>

<b>Results:</b> A significant increase in rhythmic contraction frequency was observed when superfusate from urothelium-free rabbit detrusor tissue was added to detrusor strips from the same animal. Further experiments showed that the increased rhythmic frequency induced by PGE2 was significantly reduced by pretreatment with SC-51089. In smooth muscle of arteries, dose-response experiments revealed that only TXA2 induced contraction at physiologic concentrations (< 10⁻⁷ M). Consistent with this, superfusate from detrusor tissue failed to induce tension in femoral artery segments, confirming the absence of TXA2 production. EIA results confirmed a 4.8-fold increase in PGE2 production in urothelium-free detrusor strips after 15 minutes of incubation, and this production was inhibited by both ibuprofen and a COX-1 inhibitor.<br/>

<b>Conclusions:</b> Rabbit detrusor muscle, in the absence of urothelium, produces PGE2, which appears to be the primary mediator of spontaneous rhythmic contractions (SRC). These findings suggest an intrinsic regulatory mechanism involving PGE2 in detrusor activity.
KW  - detrusor
KW  -  overactive bladder
KW  -  smooth  muscle
KW  -  prostaglandins

DO  -