Korean J Urol.  2009 Apr;50(4):396-400.

Effects of Intravesical Instillation of Antimuscarinics on Bladder Overactivity Induced by Intravesical Instillation of Adenosine Triphosphate in Rats

• Lee SB
• Lee JW
• Kim YT

Abstract

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.

Keyword

Adenosine triphosphate; Muscarinic antagonists; Rats

MeSH Terms

Adenosine
Adenosine Triphosphate
Administration, Intravesical
Anesthesia
Animals
Diamines
Female
Humans
Hydrogen-Ion Concentration
Mandelic Acids
Muscarinic Antagonists
Neurotransmitter Agents
Piperidines
Polyphosphates
Protamines
Rats
Rats, Sprague-Dawley
Receptors, Muscarinic
Urethane
Urinary Bladder
Urinary Bladder, Overactive
Urothelium
Adenosine
Adenosine Triphosphate
Diamines
Mandelic Acids
Muscarinic Antagonists
Neurotransmitter Agents
Piperidines
Polyphosphates
Protamines
Receptors, Muscarinic
Urethane

Figure

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  Fig. 1 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.

• 

  Fig. 2 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.

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