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

Kobayter, S, Young, JS and Brain, KL (2011) Prostaglandin E(2) induces spontaneous rhythmic activity in mouse urinary bladder independently of efferent nerves. Br J Pharmacol.

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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.

Item Type: Article
Divisions : Surrey research (other units)
Authors : Kobayter, S, Young, JS and Brain, KL
Date : 15 June 2011
DOI : 10.1111/j.1476-5381.2011.01543.x
Depositing User : Symplectic Elements
Date Deposited : 28 Mar 2017 15:26
Last Modified : 24 Jan 2020 11:34

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