Korean J Urol KJU Korean Journal of Urology 2005-6737 2005-6745 The Korean Urological Association 10.4111/kju.2009.50.4.396 Original Article Investigative Urology Effects of Intravesical Instillation of Antimuscarinics on Bladder Overactivity Induced by Intravesical Instillation of Adenosine Triphosphate in Rats Lee Sang Bong Lee Jae Won Kim Yong Tae Department of Urology, Hanyang University College of Medicine, Seoul, Korea. Correspondence to: Yong Tae Kim. Department of Urology, Hanyang University College of Medicine, 17, Hangdang-dong, Sungdong-gu, Seoul 133-792, Korea. TEL: 02-2290-8595, FAX: 02-2299-2186, ytkimuro@hanyang.ac.kr 04 2009 27 04 2009 50 4 396 400 17 12 2008 04 03 2009 Copyright © The Korean Urological Association, 2009 2009 Purpose

Adenosine triphosphate (ATP) from the urothelium acts as a sensory neurotransmitter and is augmented in many diseases, such as overactive bladder. We investigated the effects of intravesical instillation of oxybutynin on ATP-induced bladder overactivity to determine whether this effect is mediated by effects on urothelial muscarinic receptors.

 Materials and Methods

Cystometry (at rate of 0.04 ml/min) was performed in female Sprague-Dawley rats (body weight 250 g) under urethane anesthesia (1.2 g/kg). After a 2-hour baseline period, protamine sulfate (10 mg/ml) was instilled for 1 hour, and then ATP (60 mM, pH 6.0) or a mixture of oxybutynin (10-6 M) and ATP (60 mM, pH 6.0) was instilled intravesically. We performed experiments with 4-diphenylacetoxy-N-methylpiperidine methobromide (4-DAMP) and methoctramine by the same methods. Cystometric parameters, such as the intercontraction interval (ICI), pressure threshold (PT), and maximal voiding pressure (MVP), were compared.

 Results

With intravesical instillation of ATP after protamine sulfate treatment, the ICI was decreased compared with baseline (ICI: baseline, 487.1±64.8 s; protamine, 450.6±56.1 s; ATP, 229.7±35.3 s; p<0.05). Addition of oxybutynin, 4-DAMP, or methoctramine in the ATP solution did not significantly change the ICI compared with ATP solution alone (ICI: oxybutynin, 189.1±32.3 s; 4-DAMP, 161.1±22.8 s; methoctramine, 341.0±113.3 s; p>0.05). Intravesical instillation of ATP decreased MVP and PT significantly compared with baseline, but MVP and PT were not changed significantly with oxybutynin, 4-DAMP, or methoctramine compared with ATP.

 Conclusions

Bladder overactivity induced by intravesical instillation of ATP was not suppressed by intravesical instillation of antimuscarinics. Suppression of ATP-induced bladder overactivity by intravenous oxybutynin is not mediated by urothelial muscarinic receptors.

 Adenosine triphosphate Muscarinic antagonists Rats

This article was researched by foundation of Hanyang University investigation department (HY-2006-N).

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Typical cystometric findings. ICI decreased with intravesical ATP, but antimuscarinics did not affect the ATP-induced decrease in the ICI. (A) Oxybutynin, (B) 4-DAMP, (C) Methoctramine. ICI: intercontraction interval, ATP: adenosine triphosphate, 4-DAMP: 4-diphenylacetoxy-N-methylpiperidine methobromide.

Changes in the ICI with intravesical instillation of saline, protamine, ATP, and mixtures of ATP and antimuscarinics. The ICI was significantly decreased with intravesical instillation of ATP. Addition of oxybutynin, 4-DAMP, or methoctramine to the ATP solution did not significantly change the ICI compared with ATP solution alone. ICI: intercontraction interval, ATP: adenosine triphosphate, 4-DAMP: 4-diphenylacetoxy-N-methylpiperidine methobromide. a: p<0.05 vs. saline.

Cystometric variables with intravesical instillation of saline, protamine, and ATP with or without antimuscarinics

Data presented as Mean±SD. ATP: adenosine triphosphate, DAMP: diphenylacetoxy-N-methylpiperidine methobromide, ICI: intercontraction interval, PT: pressure threshold, MVP: maximal voiding pressure. a: p<0.05 vs. saline