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BMC Urology
Published in: BMC Urology 1/2013

Open Access 01-12-2013 | Research article

The effect of indomethacin on the muscarinic induced contractions in the isolated normal guinea pig urinary bladder

Authors: Mohammad S Rahnama’i, Gommert A van Koeveringe, Philip EV van Kerrebroeck, Stefan GG de Wachter

Published in: BMC Urology | Issue 1/2013

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Abstract

Background

To investigate the effect of prostaglandin depletion by means of COX-inhibition on cholinergic enhanced spontaneous contractions.

Methods

The urethra and bladder of 9 male guinea pigs (weight 270–300 g) were removed and placed in an organ bath with Krebs’ solution. A catheter was passed through the urethra through which the intravesical pressure was measured. The muscarinic agonist arecaidine, the non-selective COX inhibitor indomethacin, and PGE2 were subsequently added to the organ bath. The initial average frequency and amplitude of spontaneous contractions in the first 2 minutes after arecaidine application were labelled Fini and Pini, respectively. The steady state frequency (Fsteady) and amplitude (Psteady) were defined as the average frequency and amplitude during the 5 minutes before the next wash out.

Results

Application of 1 μM PGE2 increased the amplitude of spontaneous contractions without affecting frequency. 10 μM of indomethacin reduced amplitude but not frequency.
The addition of indomethacin did not alter Fini after the first application (p = 0.7665). However, after the second wash, Fini was decreased (p = 0.0005). Fsteady, Psteady and Pini were not significantly different in any of the conditions. These effects of indomethacin were reversible by PGE2 addition..

Conclusions

Blocking PG synthesis decreased the cholinergically stimulated autonomous contractions in the isolated bladder. This suggests that PG could modify normal cholinergically evoked response. A combination of drugs inhibiting muscarinic receptors and PG function or production can then become an interesting focus of research on a treatment for overactive bladder syndrome.
Appendix
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Literature
1.
Michel MC, de la Rosette JJ: Role of muscarinic receptor antagonists in urgency and nocturia. BJU Int. 2005, 96 (Suppl 1): 37-42.CrossRefPubMed
2.
3.
Griffiths D, Tadic SD: Bladder control, urgency, and urge incontinence: evidence from functional brain imaging. Neurourol Urodyn. 2008, 27 (6): 466-474. 10.1002/nau.20549.CrossRefPubMed
4.
Birder L: Role of the urothelium in bladder function. Scand J Urol Nephrol. 2004, 215: 48-53.CrossRef
5.
Pinna C, Zanardo R, Puglisi L: Prostaglandin-release impairment in the bladder epithelium of streptozotocin-induced diabetic rats. Eur J Pharmacol. 2000, 388 (3): 267-273. 10.1016/S0014-2999(99)00833-X.CrossRefPubMed
6.
Rahnama’i MS, van Kerrebroeck PE, de Wachter SG, van Koeveringe GA: The role of prostanoids in urinary bladder physiology. Nat Rev Urol. 2012, 9 (5): 283-290. 10.1038/nrurol.2012.33.CrossRefPubMed
7.
Narumiya S, Sugimoto Y, Ushikubi F: Prostanoid receptors: structures, properties, and functions. Physiol Rev. 1999, 79 (4): 1193-1226.PubMed
8.
Piper P, Vane J: The release of prostaglandins from lung and other tissues. Ann N Y Acad Sci. 1971, 180: 363-385. 10.1111/j.1749-6632.1971.tb53205.x.CrossRefPubMed
9.
Vane JR, Bakhle YS, Botting RM: Cyclooxygenases 1 and 2. Annu Rev Pharmacol Toxicol. 1998, 38: 97-120. 10.1146/annurev.pharmtox.38.1.97.CrossRefPubMed
10.
de Jongh R, van Koeveringe GA, van Kerrebroeck PE, Markerink-van Ittersum M, de Vente J, Gillespie JI: The effects of exogenous prostaglandins and the identification of constitutive cyclooxygenase I and II immunoreactivity in the normal guinea pig bladder. BJU Int. 2007, 100 (2): 419-429. 10.1111/j.1464-410X.2007.07011.x.CrossRefPubMed
11.
Maggi CA: Prostanoids as local modulators of reflex micturition. Pharmacol Res. 1992, 25 (1): 13-20. 10.1016/S1043-6618(05)80059-3.CrossRefPubMed
12.
Maggi CA, Giuliani S, Conte B, Furio M, Santicioli P, Meli P, Gragnani L, Meli A: Prostanoids modulate reflex micturition by acting through capsaicin-sensitive afferents. Eur J Pharmacol. 1988, 145 (2): 105-112. 10.1016/0014-2999(88)90221-X.CrossRefPubMed
13.
Nile CJ, de Vente J, Gillespie JI: Stretch independent regulation of prostaglandin E(2) production within the isolated guinea-pig lamina propria. BJU Int. 2009, 105 (4): 540-8.CrossRefPubMed
14.
Gillespie JI, Harvey IJ, Drake MJ: Agonist- and nerve-induced phasic activity in the isolated whole bladder of the guinea pig: evidence for two types of bladder activity. Exp Physiol. 2003, 88 (3): 343-357. 10.1113/eph8802536.CrossRefPubMed
15.
Finney SM, Stewart LH, Gillespie JI: Cholinergic activation of phasic activity in the isolated bladder: possible evidence for M3- and M2-dependent components of a motor/sensory system. BJU Int. 2007, 100 (3): 668-678. 10.1111/j.1464-410X.2007.07021.x.CrossRefPubMed
16.
McCafferty GP, Misajet BA, Laping NJ, Edwards RM, Thorneloe KS: Enhanced bladder capacity and reduced prostaglandin E2-mediated bladder hyperactivity in EP3 receptor knockout mice. Am J Physiol Renal Physiol. 2008, 295 (2): F507-F514. 10.1152/ajprenal.00054.2008.CrossRefPubMed
17.
Borda E, Contreras-Ortiz N, Gutnisky R, Gimeno MF: In vitro effect of acetylcholine and bethanechol on the contractions of the human detrusor muscle. Influence of prostaglandins. Arch Int Pharmacodyn Ther. 1982, 259 (1): 31-39.PubMed
18.
Jeremy JY, Mikhailidis DP, Dandona P: Prostanoid synthesis by the rat urinary bladder: evidence for stimulation through muscarine receptor-linked calcium channels. Naunyn Schmiedebergs Arch Pharmacol. 1986, 334 (4): 463-467. 10.1007/BF00569387.CrossRefPubMed
19.
Ishizuka O, Mattiasson A, Andersson KE: Prostaglandin E2-induced bladder hyperactivity in normal, conscious rats: involvement of tachykinins?. J Urol. 1995, 153 (6): 2034-2038. 10.1016/S0022-5347(01)67397-X.CrossRefPubMed
20.
de Jongh R, van Koeveringe GA, van Kerrebroeck PE, Markerink-van Ittersum M, de Vente J, Gillespie JI: Damage to the bladder neck alters autonomous activity and its sensitivity to cholinergic agonists. BJU Int. 2007, 100 (4): 919-929. 10.1111/j.1464-410X.2007.07129.x.CrossRefPubMed
21.
Rahnama’i MS, van Koeveringe GA, Essers PB, de Wachter SG, de Vente J, van Kerrebroeck PE, Gillespie JI: Prostaglandin receptor EP1 and EP2 site in guinea pig bladder urothelium and lamina propria. J Urol. 2010, 183 (3): 1241-1247. 10.1016/j.juro.2009.11.004.CrossRefPubMed
22.
Rahnama’i MS, de Wachter SG, van Koeveringe GA, van Kerrebroeck PE, de Vente J, Gillespie JI: The relationship between prostaglandin E receptor 1 and cyclooxygenase I expression in guinea pig bladder interstitial cells: proposition of a signal propagation system. J Urol. 2011, 185 (1): 315-322. 10.1016/j.juro.2010.09.005.CrossRefPubMed
23.
Santoso AG, Lo WN, Liang W: Urothelium-dependent and urothelium-independent detrusor contractility mediated by nitric oxide synthase and cyclooxygenase inhibition. Neurourol Urodyn. 2011, 30 (4): 619-625. 10.1002/nau.21015.CrossRefPubMed
24.
Tanaka I, Nagase K, Tanase K, Aoki Y, Akino H, Yokoyama O: Modulation of stretch evoked adenosine triphosphate release from bladder epithelium by prostaglandin E(2). J Urol. 2011, 185 (1): 341-346. 10.1016/j.juro.2010.09.042.CrossRefPubMed
25.
Collins C, Klausner AP, Herrick B, Koo HP, Miner AS, Henderson SC, Ratz PH: Potential for control of detrusor smooth muscle spontaneous rhythmic contraction by cyclooxygenase products released by interstitial cells of Cajal. J Cell Mol Med. 2009, 13 (9B): 3236-3250. 10.1111/j.1582-4934.2009.00714.x.CrossRefPubMedPubMedCentral
26.
Alkondon M, Ganguly DK: Release of prostaglandin E from the isolated urinary bladder of the guinea-pig. Br J Pharmacol. 1980, 69 (4): 573-577. 10.1111/j.1476-5381.1980.tb07906.x.CrossRefPubMedPubMedCentral
27.
Yoshida M, Masunaga K, Satoji Y, Maeda Y, Nagata T, Inadome A: Basic and clinical aspects of non-neuronal acetylcholine: expression of non-neuronal acetylcholine in urothelium and its clinical significance. J Pharmacol Sci. 2008, 106 (2): 193-198. 10.1254/jphs.FM0070115.CrossRefPubMed
28.
Andersson KE: Words of wisdom. Re: spontaneous release of acetylcholine from autonomic nerves in the bladder. Eur Urol. 2010, 57 (1): 171-172. 10.1016/j.eururo.2009.10.007.CrossRefPubMed
29.
Zagorodnyuk VP, Gregory S, Costa M, Brookes SJ, Tramontana M, Giuliani S, Maggi CA: Spontaneous release of acetylcholine from autonomic nerves in the bladder. Br J Pharmacol. 2009, 157 (4): 607-619. 10.1111/j.1476-5381.2009.00166.x.CrossRefPubMedPubMedCentral
30.
Koshita M, Hidaka K, Ueno H, Yamamoto Y, Suzuki H: Properties of acetylcholine-induced hyperpolarization in smooth muscle cells of the mouse mesenteric artery. J Smooth Muscle Res. 2007, 43 (6): 219-227. 10.1540/jsmr.43.219.CrossRefPubMed
31.
Finney SM, Andersson KE, Gillespie JI, Stewart LH: Antimuscarinic drugs in detrusor overactivity and the overactive bladder syndrome: motor or sensory actions?. BJU Int. 2006, 98 (3): 503-507. 10.1111/j.1464-410X.2006.06258.x.CrossRefPubMed
32.
Andersson KE, Yoshida M: Antimuscarinics and the overactive detrusor–which is the main mechanism of action?. Eur Urol. 2003, 43 (1): 1-5. 10.1016/S0302-2838(02)00540-7.CrossRefPubMed
33.
de Groat WC: The urothelium in overactive bladder: passive bystander or active participant?. Urology. 2004, 64 (6 Suppl 1): 7-11.CrossRefPubMed
34.
Fry CH, Ikeda Y, Harvey R, Wu C, Sui GP: Control of bladder function by peripheral nerves: avenues for novel drug targets. Urology. 2004, 63 (3 Suppl 1): 24-31.CrossRefPubMed
35.
Gillespie JI: Inhibitory actions of calcitonin gene-related peptide and capsaicin: evidence for local axonal reflexes in the bladder wall. BJU Int. 2005, 95 (1): 149-156. 10.1111/j.1464-410X.2005.05268.x.CrossRefPubMed
36.
de Jongh R, Grol S, van Koeveringe GA, van Kerrebroeck PE, de Vente J, Gillespie JI: The localisation of cyclo-oxygenase immuno-reactivity (COX I-IR) to the urothelium and to interstitial cells in the bladder wall. J Cell Mol Med. 2008, 13 (9B): 3069-81.CrossRefPubMedPubMedCentral
37.
Drake MJ, Harvey IJ, Gillespie JI, Van Duyl WA: Localized contractions in the normal human bladder and in urinary urgency. BJU Int. 2005, 95 (7): 1002-1005. 10.1111/j.1464-410X.2005.05455.x.CrossRefPubMed
38.
Kim JC, Park EY, Seo SI, Park YH, Hwang TK: Nerve growth factor and prostaglandins in the urine of female patients with overactive bladder. J Urol. 2006, 175 (5): 1773-1776. 10.1016/S0022-5347(05)00992-4. discussion 1776CrossRefPubMed
39.
Kim JC, Park EY, Hong SH, Seo SI, Park YH, Hwang TK: Changes of urinary nerve growth factor and prostaglandins in male patients with overactive bladder symptom. Int J Urol. 2005, 12 (10): 875-880. 10.1111/j.1442-2042.2005.01140.x.CrossRefPubMed
40.
Metadata
Title
The effect of indomethacin on the muscarinic induced contractions in the isolated normal guinea pig urinary bladder
Authors
Mohammad S Rahnama’i
Gommert A van Koeveringe
Philip EV van Kerrebroeck
Stefan GG de Wachter
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Urology / Issue 1/2013
Electronic ISSN: 1471-2490
DOI
https://doi.org/10.1186/1471-2490-13-8

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