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

Abstract

Isolated epithelial layer preparations were obtained from urinary bladders of 4-week streptozotocin-diabetic rats and used for endogenous prostaglandins E 2 and F 2α determination. Tissues were incubated in modified Krebs solution under basal conditions, or in the presence of either indomethacin (5×10 −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 incubation medium was under the detection limit of the enzyme immunoassay (EIA). The epithelium from diabetic rat urinary bladders was thicker and heavier and the absolute amount of endogenous prostaglandins E 2 and F 2α was higher than for control animals, but when prostaglandin production was expressed as a fraction of tissue weight, it was reduced in diabetic epithelium. ATP and bradykinin has significantly increased the endogenous release of both prostaglandins from the epithelium when compared with the release under basal conditions. This increase was time-dependent and was higher in diabetic than in control tissues. ATP evoked a phasic and tonic contraction in bladder strips that was abolished by epithelium removal. Concentration–response curves for ATP did not differ among groups. Bradykinin evoked a long-lasting tonic contraction that was reduced significantly by epithelium removal in diabetic rat bladders only. Concentration–response curves for prostaglandin E 2 and F 2α in diabetic rat bladder differed significantly from that in controls and epithelium removal did not alter these responses. It is suggested that bradykinin receptors and P2X nucleotide receptors already found in the smooth muscle detrusor might be present in the epithelial layer of the bladder. The prostaglandin-release impairment observed in this study might be responsible, in part, for bladder abnormalities observed in pathological conditions, such as diabetes.