Overactive Bladder Syndrome and the Potential Role of Prostaglandins and Phosphodiesterases: An Introduction

Rahnama’i, Mohammad Sajjad; Koeveringe, Gommert van; Kerrebroeck, Philip E. V. A. Van

doi:10.5812/numonthly.14087

Cited by 24 publications

(18 citation statements)

References 118 publications

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“…PG synthesis is initiated by several factors, as follow: 1) detrusor muscle stretching, 2) urinary bladder autonomic nerve fibers stimulation, 3) urinary bladder mucosal damage, and 4) inflammatory mediators (e.g. due to neurogenic inflammation) [5]. Numerous studies describing the effects of PGs in the urinary bladder have been published.…”

mentioning

confidence: 99%

The cardiovascular and gastrointestinal adverse effects of cyclooxygenase inhibitors seems to be a major concern that restricts their use in the treatment of urinary bladder dysfunction

Juszczak¹,

Drewa²

2015

CEJU

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Editorial referring to the paper: Gokkaya CS, Aktas BK, Ozden C, Bulut S, Karabakan M, Erkmen AE, Memis A. Flurbiprofen alone and in combination with alfuzosin for the management of lower urinary tract symptoms. Cent European J Urol. 2015; 68: 51-56.Flurbiprofen is a non-selective cyclooxygenase (COX) inhibitor, which inhibits the activity of both isoforms of COX (1 and 2). Also, flurbiprofen is one of the most potent non-steroidal anti-inflammatory agent (NSAIDs) in terms of prostaglandin inhibitory activity via reversible inhibition of COX, the enzyme responsible for the conversion of arachidonic acid to prostaglandin G2 (PGG2) and PGG2 to prostaglandin H2 (PGH2). COX exists as two isoforms, constitutive COX-1 and inducible COX-2. Prostaglandins (PGs) formed by COX-1 are primarily involved in the regulation of homeostatic functions in physiological processes, whereas PGs formed by COX-2 primarily mediate pain, inflammation, and cancer pathophysiology (e.g. prostate cancer) [1]. Aktas et al. [2] investigated the effectiveness and safety of flurbiprofen alone or in combination with alfuzosin, in the treatment of lower urinary tract symptoms suggestive of benign prostate obstruction (LUTS/BPO). The results showed that flurbiprofen increases the therapeutic effectiveness of alfuzosin by further improving symptoms in patients with LUTS/BPO. Combination therapy also improves urine flow compared to baseline. However, no superiority of monotherapy with flurbiprofen to alfuzosin is observed. Additionally, gastrointestinal adverse events are predominant in patients using flurbiprofen. PGs contribute to urinary bladder physiology. It is known that PGs are released from the urinary bladder into the general circulation in response to disThe cardiovascular and gastrointestinal adverse effects of cyclooxygenase inhibitors seems to be a major concern that restricts their use in the treatment of urinary bladder dysfunction tension. PGs originate from the urothelium and the muscle layer of the urinary bladder [3,4]. PG synthesis is initiated by several factors, as follow: 1) detrusor muscle stretching, 2) urinary bladder autonomic nerve fibers stimulation, 3) urinary bladder mucosal damage, and 4) inflammatory mediators (e.g. due to neurogenic inflammation) [5]. Numerous studies describing the effects of PGs in the urinary bladder have been published. It was reported that exogenous PGs alter urinary bladder motor activity in in vitro and in vivo studies. A link between PGs and the muscarinic system has been described previously [6]. Nile et al. [7] observed, in animal models, that ATP can activate PGE2 production by a complex mechanism, involving the purinergic receptors P2X and P2Y. Moreover, the response was inhibited by indomethacin (a non-selective COX inhibitor) and decreased the cholinergically stimulated autonomous contractions in the isolated bladder. PGs seem to affect the normal activity of the parasympathetic branch of the autonomic nervous system of the urinary bladder. In patients with overactive bladder (OAB) a hi...

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mentioning

confidence: 99%

The cardiovascular and gastrointestinal adverse effects of cyclooxygenase inhibitors seems to be a major concern that restricts their use in the treatment of urinary bladder dysfunction

Juszczak¹,

Drewa²

2015

CEJU

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“…Several investigators have shown that IC exist within DSM bundles of various mammalian species [7–9]. Previous work with rabbit DSM suggests that cyclooxygenase-mediated signaling between IC and adjacent DSM bundles may play a role in the generation of LARC via prostaglandin signaling with these findings supporting the fact that increased prostaglandin levels are seen in patients with OAB-type symptoms [24]. Others have shown that urinary bladder IC generate calcium transients that have similar frequencies to those observed in the current study suggesting IC within the bladder may be a potential source for an intrinsic bladder pacemaker [9,10].…”

Section: Discussionmentioning

confidence: 88%

Low amplitude rhythmic contraction frequency in human detrusor strips correlates with phasic intravesical pressure waves

et al. 2016

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PURPOSE Low amplitude rhythmic contractions (LARC) occur in detrusor smooth muscle and may play a role in storage disorders such as overactive bladder (OAB) and detrusor overactivity (DO). The purpose of this study was to determine whether LARC frequencies identified in vitro from strips of human urinary bladder tissue correlate with in vivo LARC frequencies, visualized as phasic intravesical pressure (pves) waves during urodynamics (UD). METHODS After IRB approval, fresh strips of human urinary bladder were obtained from patients. LARC was recorded with tissue strips at low tension (<2g) and analyzed by fast Fourier transform (FFT) to identify LARC signal frequencies. Blinded UD tracings were retrospectively reviewed for signs of LARC on the pves tracing during filling and were analyzed via FFT. RESULTS Distinct LARC frequencies were identified in 100% of tissue strips (n=9) obtained with a mean frequency of 1.97±0.47 cycles/min (33±8 mHz). Out of 100 consecutive UD studies reviewed, 35 visually displayed phasic pves waves. In 12/35 (34%), real pves signals were present that were independent of abdominal activity. Average UD LARC frequency was 2.34±0.36 cycles/min (39±6 mHz) which was similar to tissue LARC frequencies (p=0.50). A majority (83%) of the UD cohort with LARC signals also demonstrated detrusor overactivity. CONCLUSIONS During UD, a subset of patients displayed phasic pves waves with a distinct rhythmic frequency similar to the in vitro LARC frequency quantified in human urinary bladder tissue strips. Further refinements of this technique may help identify subsets of individuals with LARC–mediated storage disorders.

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“…GFP-tagged P2X3 was constructed by subcloning the full-length P2X3 cDNA into a pEGFP-N2 vector (Clontech). HA-tagged Pirt and PirtD (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) were constructed by subcloning the full-length or truncated Pirt cDNA into the pCMV-HA vector (Clontech). Full-length P2X3 cDNA was also subcloned into pcDNA3.1 3.1/myc-His( À ) A (Invitrogen).…”

Section: Methodsmentioning

confidence: 99%

“…In response to physical and chemical stimulation, the urothelium releases several substances, including acetylcholine, ATP, prostaglandins and so on [6][7][8] . These chemical agents modify afferent nerve activity and sensation in the suburothelial layer and in the muscle layer 2 .…”

mentioning

confidence: 99%

Pirt reduces bladder overactivity by inhibiting purinergic receptor P2X3

et al. 2015

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Pirt is a transmembrane protein predominantly expressed in peripheral neurons. However, the physiological and pathological roles of Pirt in hollow viscus are largely unknown. Here we show that Pirt deficiency in mice causes bladder overactivity. The density of a,b-meATP-induced currents is significantly reinforced in Pirt-deficient dorsal root ganglion (DRG) neurons. Pirt and P2X3 receptor co-localize in bladder nerve fibres and heterologous Pirt expression significantly reduces P2X3-mediated currents. Pirt interacts with P2X3 through the N-terminal 14 amino-acid residues. TAT-conjugated Pirt N14 peptide (Pirt N14 ) is sufficient to inhibit P2X3 activation in bladder DRG neurons and to alleviate bladder overactivity in Pirt À / À mice. Pirt expression is decreased in the bladder of cyclophosphamide (CYP)-treated mice, a commonly used model of bladder overactivity. Importantly, Pirt N14 administration reduces the frequency of bladder voiding and restores the voided volume of CYP-treated mice. Therefore, our results demonstrate that Pirt is an endogenous regulator of P2X3 in bladder function.

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Overactive Bladder Syndrome and the Potential Role of Prostaglandins and Phosphodiesterases: An Introduction

Cited by 24 publications

References 118 publications

The cardiovascular and gastrointestinal adverse effects of cyclooxygenase inhibitors seems to be a major concern that restricts their use in the treatment of urinary bladder dysfunction

The cardiovascular and gastrointestinal adverse effects of cyclooxygenase inhibitors seems to be a major concern that restricts their use in the treatment of urinary bladder dysfunction

Low amplitude rhythmic contraction frequency in human detrusor strips correlates with phasic intravesical pressure waves

Pirt reduces bladder overactivity by inhibiting purinergic receptor P2X3

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