Present address: Faculty of Health and Medical Sciences, Wolfson Cell Science Building, University of Surrey, Guildford, Surrey GU2 7XH, UK.
Prostaglandin E2 induces spontaneous rhythmic activity in mouse urinary bladder independently of efferent nerves
Version of Record online: 16 DEC 2011
© 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society
British Journal of Pharmacology
Volume 165, Issue 2, pages 401–413, January 2012
How to Cite
Kobayter, S., Young, J. and Brain, K. (2012), Prostaglandin E2 induces spontaneous rhythmic activity in mouse urinary bladder independently of efferent nerves. British Journal of Pharmacology, 165: 401–413. doi: 10.1111/j.1476-5381.2011.01543.x
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- Issue online: 16 DEC 2011
- Version of Record online: 16 DEC 2011
- Accepted manuscript online: 15 JUN 2011 02:05AM EST
- Received; 26 July 2010; Revised; 19 April 2011; Accepted; 1 June 2011
- prostaglandin E;
- urinary bladder;
- smooth muscle;
- parasympathetic nervous system
BACKGROUND AND PURPOSE The acute effects of PGE2 on bladder smooth muscle and nerves were examined to determine the origin of PGE2-induced spontaneous rhythmic contractions.
EXPERIMENTAL APPROACH Contraction studies, confocal Ca2+ imaging and electrophysiological recordings in strips of mouse urinary bladder were used to differentiate the effects of PGE2 on bladder smooth muscle and efferent nerves.
KEY RESULTS PGE2 (50 µM) increased the tone and caused phasic contractions of detrusor smooth muscle strips. Confocal Ca2+ imaging showed that PGE2 increased the frequency of whole-cell Ca2+ transients (WCTs) (72 ± 5%) and intracellular recordings showed it increased the frequency of spontaneous depolarizations, from 0.31·s−1 to 0.90·s−1. Non-selective inhibition of EP receptors using SC-51322 and AH-6809 (10 µM), or the L-type Ca2+ channel blocker nifedipine (1 µM), prevented these phasic contractions and WCTs, and reduced the tone (by 45 ± 7% and 59 ± 6%, respectively). Blocking P2X1 receptors with NF449 (10 µM) caused a small but significant reduction in the frequency of PGE2-induced phasic contractions (24 ± 9%) and WCTs (28 ± 17%) but had no significant effect on spontaneous depolarizations or tone. Inhibiting muscarinic receptors with cyclopentolate (1 µM) had no significant effect on these measures. Spontaneous WCTs became synchronous in PGE2, implying enhanced functional coupling between neighbouring cells. However, the electrical input resistance was unchanged.
CONCLUSIONS AND IMPLICATIONS It was concluded that depolarization alone is sufficient to explain a functional increase in intercellular coupling and the ability of PGE2 to increase detrusor spontaneous rhythmic activity does not require parasympathetic nerves.