ICS
1999, Denver
Informally discussed
posters
Pharmacology
Prostaglandin-linked,
ATP-induced post-tonic contraction increases with age in rat urinary bladder
detrusor muscle
Kageyama S., Shinbo H.,
Hayami S., Watanabe T., Suzuki K., Fujita K.
Department of Urology,
Hamamatsu University School of Medicine, 3600 Hanada-cho, Hamamatsu, Japan
Aims of Study: To study the age-related changes (1-3) of bladder function, we investigated the recently discovered "ATP-induced post-tonic contraction" in rats of various ages.
Materials and Methods: Urinary bladders were obtained from male Wistar rats at the ages of 9 weeks [young], 24 weeks [adult], and 24 months [aged]. After rats were sacrificed with an intraperitoneal injection of pentobarbital, ATP-induced contraction of resected urinary bladder muscle strips were measured isometrically. A contractile response was induced by adding 10-4M ATP to the organ bath. The strip was then washed with K-H solution and relaxed to baseline, after which a second contraction began. We defined this second contraction as post-tonic contraction. All strips examined phasic (99.1%; n=111) and post-tonic (91.6%; n=105) contraction greater than 0.1g/tension of tissue were utilized in the present investigation. The magnitude of ATP-induced phasic and post-tonic contraction was compared between age groups.
Results: ATP-induced post-tonic contraction did not occur after stimulation with KCI or acetylcholine, but was induced by ð , ð -methylene ATP. Both phasic and post-tonic contraction were concentration dependent. Although phasic contraction was decreased in aged rats, the magnitude and duration of post-tonic contraction were greatest in aged rats followed by adult and then young rats aged. Nicardipine (a calcium antagonist) showed a slight inhibitory effect on both contractions. Suramin ( a non-selective P2 receptor antagonist) inhibited phasic contraction, but did not influence post-tonic contraction. PPADS ( a selective P2x receptor antagonist) did not inhibit phasic or post-tonic contraction. In contrast, indomethacin (a prostaglandin synthesis inhibitor) almost completely blocked post-tonic contraction, when added 20 minutes prior to ATP stimulation.
Conclusion: These findings suggest that ATP-induced post-tonic contraction is not mediated by the P2x purinoceptor, and that prostaglandin is related to it. Post-tonic contraction was significantly stronger and more persistent in aged rats than in younger rats. This phenomenon may have a close relationship to the adverse changes of the urinary bladder that occur with aging.
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