Urea modifies the permeability of the mammalian urothelium

Purpose: This study investigated the effects of mucosal (urine side) and se rosal (blood side) urea on the permeability properties of the in vitro mamm alian urinary bladder epithelium. Materials and Methods: The permeability properties of the rabbit urinary bl adder epithelium were studied in modified Ussing chambers using electrophys iological techniques. Results: Addition of two molar urea to the mucosal solution did not cause a significant change in the short circuit current (I-sc, a measure of the io n transport capacity of the epithelium), or the transepithelial conductance (G(t), a measure of the ability of ions to diffuse across the epithelium). In contrast, addition of 0.5 M urea to the serosal solution caused an incr ease in G(t) of similar to 35 mu S/cm.(2) as well as an increase in I-sc ov er a 5 minute period. The site of the conductance increase by short-term se rosal urea was at the apical membrane and not at the tight junctions. The u rea-induced conductance completely reversed upon removal of urea, was non-s elective, and the magnitude was voltage dependent. Long term serosal urea ( greater than 30 minutes) resulted in an irreversible increase in transepith elial conductance. Mucosal urea altered the time course but not the magnitu de of the serosal urea-induced conductance. Conclusions: The ion permeability of the mammalian urinary bladder is incre ased by serosal urea. At short times the increase is at the apical membrane , while at long times the increase is at the tight junctions. The presence of mucosal urea slows the loss of urothelial barrier function caused by ser osal urea.