Effects of Intravesical Instillation of Antimuscarinics on Bladder Overactivity Induced by Intravesical Instillation of Adenosine Triphosphate in Rats.
10.4111/kju.2009.50.4.396
- Author:
Sang Bong LEE
1
;
Jae Won LEE
;
Yong Tae KIM
Author Information
1. Department of Urology, Hanyang University College of Medicine, Seoul, Korea. ytkimuro@hanyang.ac.kr
- Publication Type:Original Article
- Keywords:
Adenosine triphosphate;
Muscarinic antagonists;
Rats
- MeSH:
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
- From:Korean Journal of Urology
2009;50(4):396-400
- CountryRepublic of Korea
- Language:Korean
-
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.