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ID 32958
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Author
Nishiguchi, Jun
Hayashi, Yukio
Chancellor, Michael B
de Miguel, Fernando
de Groat, William C
Yoshimura, Naoki
Abstract

Objectives.
We investigate the effects of intravesical application of adenosine 5'-triphosphate (ATP) on bladder activity to elucidate the role of urothelial barrier function and ecto-ATPase activity in the ATP-mediated mechanism inducing detrusor overactivity.

Methods.
Continuous cystometry by an intravesical catheter inserted from the bladder dome was performed in conscious female rats.

Results.
ATP solutions adjusted to pH 6.0 did not elicit significant detrusor overactivity at a concentration of 60 mM. However, in bladders pretreated with protamine sulfate (10 mg/mL) to increase urothelial permeability, ATP solution (pH 6.0) induced detrusor overactivity by decreasing the intercontraction intervals. These irritant effects of ATIP after protamine treatment were antagonized by P2X receptor antagonists, such as pyridoxal-5-phosphate-6-azophenyl-2',4-disulfonic acid (70 mu mol/kg) and 2',3'-O-(2,4,6, trinitrophenyl) ATP (30 mu mol/kg). These were also suppressed in rats pretreated with systemic capsaicin (125 mg/kg subcutaneously). Alpha,beta-methylene ATP (5 mM, pH 6.0) or ATP (60 mM, pH6) after intravesical infusion of 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (5 mM, pH 6.0), an ecto-ATPase inhibitor, induced detrusor overactivity without protamine pretreatment, but the reduction in intercontraction intervals was smaller compared with that with ATP after protamine treatment.

Conclusions.
Low permeability of bladder epithelium and ecto-ATPase activity can prevent ATP activation of subepithelial P2X receptors to induce bladder overactivity. Thus, enhanced penetration of endogenous ATIP owing to urothelial damage may contribute to urinary frequency and bladder pain in hypersensitive bladder disorders such as interstitial cystitis.

Keywords
P2X receptors
urinary bladder
C-fiber
Note
Digital Object Identifer:10.1016/j.urology.2005.06.099
Published with permission from the copyright holder. This is the institute's copy, as published in Urology, December 2005, Volume 66, Issue 6, Pages 1332-1337.
Publisher URL:http://dx.doi.org/10.1016/j.urology.2005.06.099
Direct access to Thomson Web of Science record
Copyright © 2005 Elsevier Inc. All rights reserved.
Published Date
2005-12
Publication Title
Urology
Volume
volume66
Issue
issue6
Start Page
1332
End Page
1337
Content Type
Journal Article
language
英語
Refereed
True
DOI
Web of Science KeyUT
Submission Path
urology/1