Prostaglandin-release impairment in the bladder epithelium of streptozotocin-induced diabetic rats

Isolated epithelial layer preparations were obtained from urinary bladders of 4-week streptozotocin-diabetic rats and used for endogenous prostaglandi ns E-2 and F-2 alpha determination. Tissues were incubated in modified Kreb s solution under basal conditions, or in the presence of either indomethaci n (5 x 10(-7) M), ATP (10(-5) and 10(-3) M) or bradykinin (10(-7) and 10(-5 ) M), and samples of incubation medium were collected at 15 and 30 min. In the presence of indomethacin, the release of prostaglandins in the incubati on medium was under the detection Limit of the enzyme immunoassay (EIA). Th e epithelium from diabetic rat urinary bladders was thicker and heavier and the absolute amount of endogenous prostaglandins E-2 and F-2 alpha was hig her than for control animals, but when prostaglandin production was express ed as a fraction of tissue weight, it was reduced in diabetic epithelium. A TP and bradykinin has significantly increased the endogenous release of bot h prostaglandins from the epithelium when compared with the release under b asal conditions. This increase was time-dependent and was higher in diabeti c than in control tissues. ATP evoked a phasic and tonic contraction in bla dder strips that was abolished by epithelium removal. Concentration-respons e curves for ATP did not differ among groups. Bradykinin evoked a long-last ing tonic contraction that was reduced significantly by epithelium removal in diabetic rat bladders only. Concentration-response curves for prostaglan din E-2 and F-2 alpha in diabetic rat bladder differed significantly from t hat in controls and epithelium removal did not alter these responses. It is suggested that bradykinin receptors and P2X nucleotide receptors already f ound in the smooth muscle detrusor might be present in the epithelial layer of the bladder. The prostaglandin-release impairment observed in this stud y might be responsible, in part, for bladder abnormalities observed in path ological conditions, such as diabetes. (C) 2000 Elsevier Science B.V. All r ights reserved.