Abstract

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• INTRODUCTION:

  The purpose of this investigation was to determine if prostaglandin E₂ (PGE₂) is produced by rabbit detrusor free of urothelium and demonstrate that PGE₂ is responsible for the generation of spontaneous rhythmic contraction (SRC). METHODS: A bioassay was performed in which contraction frequency in strips of rabbit detrusor was compared before and after addition of superfusate from incubating sections of rabbit detrusor. Specificity was determined by testing the effects of SC-51089, a PGE₂ (EP1) antagonist. Effects on development of tension were determined in artery segments after treatment with increasing doses of PGE₂, PGF₂α, and TXA₂, and a section of femoral artery was used as a negative control. Confirmation of PGE2 production was then determined using EIA kits.

  RESULTS:

  Increased rhythmic frequency was identified after superfusate from a section of rabbit detrusor free of urothelium was added to strips of detrusor from the same animal. Additional experiments demonstrated that rhythmic frequency generated after treatment with PGE₂ was significantly reduced after treatment with SC-51089. In artery smooth muscle, prostaglandin dose response experiments demonstrated that only TXA₂ induced contraction at physiologic doses (<10⁻ ⁷M). As a negative control, subsequent treatment of a section of femoral artery with detrusor superfusate failed to increase tension, confirming a lack of TXA2 production. EIA confirmed that PGE₂ production increased by 4.8-fold in strips of detrusor free of urothelium after 15 minutes of incubation and that this production was blocked by ibuprofen and a COX-1 inhibitor.

  CONCLUSIONS:

  Rabbit detrusor produces PGE₂ which is the most likely mediator of SRC.