Toggle Main Menu Toggle Search

Open Access padlockePrints

Phosphodiesterase-linked inhibition of nonmicturition activity in the isolated bladder

Lookup NU author(s): Professor James Gillespie


Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


OBJECTIVE: To explore the influence of intracellular cAMP on phasic activity in the isolated bladder (phasic rises in intravesical pressure associated with waves of contraction and local stretches that can be activated by muscarinic or nicotinic agonists), as it has been argued that this activity underlies nonmicturition contractions, and that it contributes to the generation and modulation of afferent nerve activity. MATERIALS AND METHODS: Isolated whole bladders from female guinea pigs (270-300 g) were cannulated via the urethra and suspended in a chamber containing oxygenated Tyrode solution at 33-35°C. Bladder pressure was recorded and pharmacological agents added to the solution bathing the abluminal surface of the bladder. RESULTS: Forskolin (1-3 μmol/L), an activator of adenyl cyclase, reduced the frequency and amplitude of the phasic activity induced by the muscarinic agonist arecaidine (300 nmol/L). There were similar changes in frequency and amplitude in bladders exposed to the nonspecific phosphodiesterase (PDE) inhibitor iso-butyl-methyl-xanthene (IBMX). The actions of specific PDE inhibitors were explored to assess which isoenzymes might be responsible for regulating phasic activity. ENHA (PDE-2), zaprinast (PDE-5, -6, -8, -9 and -11) and siguazodan (PDE-3) had no effect. Zardavarine (PDE-3, -4) and Ro 20-1724 (PDE-4) reduced both the frequency and amplitude of the phasic activity. Nerve-mediated rises in intravesical pressure were also inhibited by Ro 20-1724, and the inhibition was more pronounced at 6.5 Hz than at 30 Hz stimulation. Ro 20-1724 inhibited nerve-mediated fluctuations induced by prolonged (200 s) stimulation at 6.5 Hz. CONCLUSION: The mechanisms influencing the frequency of agonist-induced phasic activity in the isolated bladder are slowed by cAMP. Degradation of intracellular cAMP in the cells responsible for phasic activity appears to involve primarily PDE-4. The importance of these observations in relation to the overall physiological regulation of the bladder are discussed, and the possible importance of these findings in the development of pharmacological strategies to modulated bladder activity reviewed.

Publication metadata

Author(s): Gillespie JI

Publication type: Article

Publication status: Published

Journal: BJU International

Year: 2004

Volume: 93

Issue: 9

Pages: 1325-1332

ISSN (print): 1464-4096

ISSN (electronic): 1464-410X

Publisher: Wiley-Blackwell Publishing Ltd.


DOI: 10.1111/j.1464-410X.2004.04840.x

PubMed id: 15180632


Altmetrics provided by Altmetric