NDLI: Potential for control of detrusor smooth muscle spontaneous rhythmic contraction by cyclooxygenase products released by interstitial cells of Cajal

Content Provider	PubMed Central
Author	Collins, Clinton Klausner, Adam P. Herrick, Benjamin Koo, Harry P. Miner, Amy S. Henderson, Scott C. Ratz, Paul H.
Copyright Year	2009
Abstract	Interstitial cells of Cajal (ICCs) have been identified as pacemaker cells in the upper urinary tract and urethra, but the role of ICCs in the bladder remains to be determined. We tested the hypotheses that ICCs express cyclooxygenase (COX), and that COX products (prostaglandins), are the cause of spontaneous rhythmic contraction (SRC) of isolated strips of rabbit bladder free of urothelium. SRC was abolished by 10 μM indomethacin and ibuprofen (non-selective COX inhibitors). SRC was concentration-dependently inhibited by selective COX-1 (SC-560 and FR-122047) and COX-2 inhibitors (NS-398 and LM-1685), and by SC-51089, a selective antagonist for the PGE-2 receptor (EP) and ICI-192,605 and SQ-29,548, selective antagonists for thromboxane receptors (TP). The partial agonist/antagonist of the PGF-2α receptor (FP), AL-8810, inhibited SRC by ∼50%. Maximum inhibition was ∼90% by SC-51089, ∼80–85% by the COX inhibitors and ∼70% by TP receptor antagonists. In the presence of ibuprofen to abolish SRC, PGE-2, sulprostone, misoprostol, PGF-2α and U-46619 (thromboxane mimetic) caused rhythmic contractions that mimicked SRC. Fluorescence immunohistochemistry coupled with confocal laser scanning microscopy revealed that c-Kit and vimentin co-localized to interstitial cells surrounding detrusor smooth muscle bundles, indicating the presence of extensive ICCs in rabbit bladder. Co-localization of COX-1 and vimentin, and COX-2 and vimentin by ICCs supports the hypothesis that ICCs were the predominant cell type in rabbit bladder expressing both COX isoforms. These data together suggest that ICCs appear to be an important source of prostaglandins that likely play a role in regulation of SRC. Additional studies on prostaglandin-dependent SRC may generate opportunities for the application of novel treatments for disorders leading to overactive bladder.
Related Links	http://dx.doi.org/10.1111/j.1582-4934.2009.00714.x
Ending Page	3250
Page Count	15
Starting Page	3236
File Format	PDF
ISSN	15821838
e-ISSN	15824934
Journal	Journal of Cellular and Molecular Medicine
Issue Number	9b
Volume Number	13
Language	English
Publisher	John Wiley & Sons, Ltd
Publisher Date	2009-02-01
Access Restriction	Open
Rights Holder	John Wiley & Sons, Ltd
Subject Keyword	Molecular Medicine Cell Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Molecular Medicine

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