Effect of age on the responses of rat bladder detrusor strips to adenosine triphosphate.
OBJECTIVE
To assess age-related changes in bladder function using the contractile responses to ATP of detrusor strips from rats of various ages. Materials and methods Urinary bladders were obtained from male Wistar rats aged 9 weeks (young), 24 weeks (adult) and 24 months (aged). Contractions of urinary bladder muscle strips to ATP were measured isometrically. The size of the initial phasic response and the secondary contractile response that developed after washing out ATP (postwashout contraction) were measured. The magnitudes of the ATP-induced phasic and postwashout contraction were compared among the age groups. During the contractions, prostanoid concentrations in the organ-bath medium were measured using an enzyme immunoassay.


RESULTS
The ATP-induced postwashout contraction did not occur after stimulation with KCl or acetylcholine, but was induced by alpha,beta-methylene ATP. Both the phasic and postwashout contractions were concentration-dependent. Although the phasic contraction did not change progressively with age, the magnitude and duration of the postwashout contraction increased substantially with age. Nicardipine (a calcium antagonist) slightly inhibited both contractions. Suramin (a nonselective P2-receptor antagonist) did not significantly inhibit the phasic contraction, but reduced the postwashout contraction. PPADS (a selective P2X receptor antagonist) did not inhibit either contraction. Indomethacin (a prostaglandin synthesis inhibitor) had no effect on the phasic contraction but almost completely blocked the postwashout contraction when added before ATP stimulation, but was less effective when added after ATP. The prostaglandin E2 concentration in the organ bath increased during the postwashout contraction.


CONCLUSIONS
These findings suggest that the ATP-induced postwashout contraction is not directly mediated by P2x purinoceptors, but results from the synthesis of prostaglandins, especially E2, which is a sensory autacoid. The age-linked increase in postwashout contraction may be involved in the changes in sensory and voiding mechanisms seen in the aged urinary bladder.
Kageyama
S
S
Department of Urology, Hamamatsu University School of Medicine, Hamamatsu, and Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co. Ltd, Tsukuba, Japan. kage3309@hama-med.ac.jp
Fujita
K
K
Suzuki
K
K
Shinbo
H
H
Masuda
N
N
Uchida
W
W
D000109:Acetylcholine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000375:Aging / Q000502:physiology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009529:Nicardipine / Q000494:pharmacology; D058914:Purinergic Antagonists; D051381:Rats; D017208:Rats, Wistar; D001743:Urinary Bladder / Q000187:drug effects*
D058914:Purinergic Antagonists; D004533:Egtazic Acid; D000255:Adenosine Triphosphate; D009529:Nicardipine; D000109:Acetylcholine