Abstract

BackgroundInflammation is often associated with several bladder dysfunctions, including overactive bladder (OAB) and interstitial cystitis/bladder pain syndrome (IC/PBS). As such, inflammation of the bladder and the actions of inflammatory mediators may contribute to the development of urinary symptoms. This study assessed the actions of PGE2, PGF2, PGD2, TXA2, and PGI2 on urinary bladder urothelium with lamina propria (U&LP), and detrusor smooth muscle.MethodsStudies were carried out using isolated tissue baths, where strips of porcine bladder U&LP or detrusor were exposed to varying concentrations of prostaglandin agonists (1 μM and 10 μM).ResultsAll assessed prostaglandin agonists contracted both the U&LP and detrusor smooth muscle, with the rank order of contractile response effectiveness as: PGE2 > PGF2α > TXA2 > PGD2 > PGI2. In U&LP, treatment with PGE2 (10 μM) increased tonic contractions by 1.36 ± 0.09 g (n = 42, p < 0.001) and phasic contractions by 40.4 ± 9.6% (n = 42, p < 0.001). In response to PGF2α (10 μM), U&LP tonic contractions increased by 0.79 ± 0.06 g (n = 14, p < 0.001) and phasic activity by 13.3% ± 5.3% (n = 15, p < 0.05). In detrusor preparations, PGE2 (10 μM) increased tonic contractions by 1.32 ± 0.13 g (n = 38, p < 0.001) and PGF2α (10 μM) by 0.97 ± 0.14 g (n = 12, p < 0.001). Only 34% (n = 48) of all detrusor preparations exhibited spontaneous activity prior to the addition of any agonist at a frequency of 2.03 ± 0.12 cpm. In preparations that did not exhibit initial phasic activity, all of the prostaglandin agonists were capable of commencing phasic activity.ConclusionsThe urinary bladder U&LP and detrusor respond to a variety of prostaglandin agonists, with their activation resulting in direct contractions, as well as increases to spontaneous contractile activity. This study presents the prostaglandin receptor system as a potential therapeutic target for lower urinary tract dysfunction.

Highlights

  • Inflammation is often associated with several bladder dysfunctions, including overactive bladder (OAB) and interstitial cystitis/bladder pain syndrome (IC/PBS)

  • Urothelium with lamina propria was dissected from the underlying detrusor layer, consistent with methods carried out in past studies [18,19,20,21], and cut in strips

  • PGE2 (1 μM) was added to isolated tissues, spontaneous activity increased by 39.2% ± 6.7% (n = 38, p < 0.001, Fig. 1)

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Summary

Introduction

Inflammation is often associated with several bladder dysfunctions, including overactive bladder (OAB) and interstitial cystitis/bladder pain syndrome (IC/PBS). This study assessed the actions of PGE2, PGF2, PGD2, TXA2, and PGI2 on urinary bladder urothelium with lamina propria (U&LP), and detrusor smooth muscle. Prostaglandin production is generally low in healthy tissue but can increase immediately following acute inflammation [8]. They are synthesised in the bladder by cyclooxygenase (COX) and subsequently converted into five primary prostanoids via their respective synthases: PGE2, PGD2, PGF2α, prostacyclin (PGI2) and thromboxane (TXA2) [9]. Prostaglandins are synthesised in both the bladder urothelium with lamina propria (U&LP) and in detrusor smooth muscle in response to stretch, nerve stimulation, U&LP damage or other inflammatory mediators [10, 11]. Prostaglandin I2 is the main prostaglandin synthesised in the human bladder, followed by PGE2, PGF2α and TXA2 [14, 15]

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