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KMID : 0358320090500040396
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Korean Journal of Urology
2009 Volume.50 No. 4 p.396 ~ p.400
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Effects of Intravesical Instillation of Antimuscarinics on Bladder Overactivity Induced by Intravesical Instillation of Adenosine Triphosphate in Rats
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Lee Sang-Bong
Lee Je-Won
Kim Yong-Tae
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Abstract
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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.
Conslusions: 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
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KEYWORD
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Adenosine triphosphate, Muscarinic antagonists, Rats
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