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67th Annual Meeting Abstracts
Prostaglandin Production By Interstitial Cells Of Cajal Regulates Spontaneous Rhythmic Contraction Of The Urinary Bladder
Corey M Johnson, *Clinton Collins, *Vikram Sabarwal, *Aaron Sitke, *Amy S Miner, *Paul H Ratz, Harry P Koo, Adam P Klausner
VCUHS, Richmond, VA
Introduction:
Bladders from patients and animals with overactive bladder display increased spontaneous rhythmic contraction(SRC). We tested the hypothesis that Interstitial Cells of Cajal(ICC) express cyclooxygenase(COX) and produce prostaglandins that cause SRC.
Materials & Methods:
In muscle experiments using strips of rabbit detrusor free of urothelium, SRC was measured after addition of COX inhibitors and prostaglandin receptor antagonists. Fluorescence immunohistochemistry with scanning confocal microscopy investigated the presence of ICC in bladder and COX. Using enzyme immunoassay(EIA), PGE2 production was determined in tissues incubated for 1, 5, and 15 minutes in physiologic salt solution, and effects on production were studied after pre-treatment with COX inhibitors.
Results:
Maximum inhibition of SRC was achieved with a selective PGE2 receptor antagonist(~90%) with slightly less inibition achieved using COX inhibitors(~80-85%). Confocal microscopy revealed that ICC markers(c-Kit and vimentin) co-localized to cells surrounding detrusor smooth muscle(DSM) bundles(Fig1, purple with blue nuclei), indicating the presence of extensive ICC. COX-1(Fig1-yellow/orange) and COX-2 co-localized with interstitial cells expressing vimentin, an ICC marker. EIA analysis revealed a 4.8 fold increase in PGE2 production at 15 minutes(p<0.05). PGE2 production was reduced by pre-treatment a non-selective COX inhibitor(ibuprofen: 88%, p<0.05), COX-1 inhibitor(SC560: 45%, p<0.05) and COX-2 inhibitor(NS-398: 47%, p=0.065).
Conclusions:
These data suggest that basal synthesis of prostaglandins by COX-1 and COX-2, expressed by ICC, regulates SRC. Additional studies may identify novel targets for the treatment of overactive bladder.
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