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Role of rat urinary bladder interstitial cells in neurogenic detrusor overactivity
Author(s) -
Ikeda Youko,
Kanai Anthony
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.816.4
Subject(s) - urinary bladder , connexin , overactive bladder , receptor , endocrinology , medicine , immunohistochemistry , chemistry , vimentin , cd34 , urinary system , urology , gap junction , pathology , biology , stem cell , microbiology and biotechnology , biochemistry , intracellular , alternative medicine
We have previously identified an increase in number and gap junction connectivity (connexin 43) of interstitial cells (ICs) in the urinary bladders of spinal cord transected (SCT) rats. Our data suggest that these ICs drive the enhanced spontaneous contractions responsible for neurogenic detrusor overactivity. In this study, we further characterized the changes in ICs that may contribute to this overactivity. ICs were identified through immunohistochemistry using vimentin and CD34 as IC‐markers. ICs form an extensive network throughout the bladder wall with a dense plexus in the suburothelium. In bladders from SCT rats, there was also a significant increase in the expression of P2Y 6 and c ‐kit receptors on ICs, particularly in the suburothelium. The amplitude of spontaneous contractions from in vitro tension recordings of SCT rat whole bladders sheet preparations (1.3±0.9 g/mm 2 , n=9) were decreased by the addition of 30 μM Gleevec ( c ‐kit receptor inhibitor, 52.5±16.0% reduction, n=6) and 10 μM MRS2578 (P2Y 6 ‐antagonist, 34.8±18.6% reduction, n=4) to the superfusion solution. However, no effect on spontaneous contractions of normal adult bladder preparations was seen with these compounds (0.3±0.2 g/mm 2 , n=6). These functional results correlated with immunohistochemical data showing increased number of ICs and the involvement of P2Y 6 and c ‐kit receptors in detrusor overactivity following SCT. In summary, increased functionality of ICs has a contributory role in neurogenic detrusor overactivity and may represent a potential therapeutic target. This research was sponsored by awards from Pfizer Ltd.