Mechanical trauma to bladder epithelium liberates prostanoids which modulate neurotransmission in rabbit detrusor...

Transitional epithelium of the rabbit urinary bladder has been implicated as a major site of prostanoid production and various studies have indicated that prostanoids have significant influences in muscle activity and neurotransmission in the bladder. We have examined the possibility that mechanical irritation of the epithelium could release diffusable substances which could influence neuromuscular function in the bladder. Epithelium was dissected from muscle strips of rabbit urinary bladder and the two components were incubated in separate chambers. Krebs' solution bathing epithelium was transferred to the bath in which the muscle was being field stimulated. Increases in the basal tension and spontaneous activity of the muscle as well as in the electrically evoked responses were observed after transfer and were related to the intensity of the irritation given the epithelium sample. The effects were mimicked by prostaglandins E1 E2, F2 alpha and I2 and the transfer effect was reduced significantly by pretreatment of the epithelium, but not the muscle, with indomethacin (10 microM) or ibuprofen (100 microM). Transfer of solution bathing-irritated epithelium also raised basal tension but not the maximum response to bethanechol. Finally, radioimmunoassay was used to demonstrate that irritation of epithelium samples caused the appearance of prostaglandin and 6-oxo-prostaglandin F1 alpha in the bathing medium and that this appearance was profoundly depressed by indomethacin (10 microM). It is plausible, therefore, that mechanical irritation of the bladder epithelium could result in changes in neuromuscular function in the underlying muscle layers and that these changes would be consistent with the symptoms associated with mechanical trauma of urothelium.