Prostaglandin E 2 induces spontaneous rhythmic activity in mouse urinary bladder independently of efferent nerves

S. Kobayter, J. S. Young, K. L. Brain

Research output: Contribution to journalArticlepeer-review

Abstract

Background and Purpose The acute effects of PGE 2 on bladder smooth muscle and nerves were examined to determine the origin of PGE 2-induced spontaneous rhythmic contractions. Experimental APPROACH Contraction studies, confocal Ca 2+ imaging and electrophysiological recordings in strips of mouse urinary bladder were used to differentiate the effects of PGE 2 on bladder smooth muscle and efferent nerves. Key Results PGE 2 (50 μM) increased the tone and caused phasic contractions of detrusor smooth muscle strips. Confocal Ca 2+ imaging showed that PGE 2 increased the frequency of whole-cell Ca 2+ 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 Ca 2+ 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 PGE 2-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 PGE 2, 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 PGE 2 to increase detrusor spontaneous rhythmic activity does not require parasympathetic nerves. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.
Original languageEnglish
Pages (from-to)401-413
Number of pages13
JournalBritish Journal of Pharmacology
Volume165
Issue number2
DOIs
Publication statusPublished - 15 Jun 2011
Externally publishedYes

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