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

S Kobayter, JS Young, Keith Brain

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16 Citations (Scopus)
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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 electrophysiology in strips of mouse urinary bladder. Key Results:  Detrusor smooth muscle strips generated a PGE(2)  (50 µM)-induced increase in tone and phasic contractions, a characteristic of detrusor overactivity. Confocal Ca(2+) imaging showed a PGE(2) -induced increase in the frequency of whole cell Ca(2+) transients (WCTs) (72 ± 5%) and intracellular recordings showed an increased 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 phasic contractions and WCTs, and reduced the tone (by 45 ± 7% and 59 ± 6% respectively). Blocking P2X(1) 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 (median control 181 MΩ; PGE(2) median 209 MΩ). Conclusions and Implications:  It is argued that depolarization alone is sufficient to explain a functional increase in intercellular coupling. The action of PGE(2 ) to increase detrusor spontaneous rhythmic activity does not require parasympathetic nerves.
Original languageEnglish
Pages (from-to)401-413
Number of pages13
JournalBritish Journal of Pharmacology
Volume165
Issue number2
Early online date16 Dec 2011
DOIs
Publication statusPublished - 1 Jan 2012

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