IN-VITRO FLUID SECRETION BY EPITHELIUM FROM POLYCYSTIC KIDNEYS

The size of the kidneys in patients with autosomal dominant polycystic kidney disease (ADPKD) is due in large measure to the accumulation of secreted fluid within thin-walled epithelial sacs. We measured the ne t transepithelial movement of liquid in response to forskolin in isola ted, intact cysts excised from the surface of human ADPKD kidneys and in cultured, polarized monolayers of epithelial cells derived from ADP KD cysts, 10 excised cysts bathed symmetrically in control culture med ium secreted fluid at a rate of 0.19+/-0.03 mu l/cm(2) per hour after stimulation with forskolin (10 mu M). Ouabain (100 mu M) addition to t he cavity fluid did not change the rate of fluid secretion of 10 forsk olin-treated cysts, but addition of the glycoside to the external bath ing medium fluid of nine cysts decreased secretion to -0.004+/-0.05 mu l/cm(2) per hour, 24 monolayers absorbed fluid (range -0.029 to -0.41 2 mu l/cm(2) per hour); by contrast, fluid was secreted (range 0.074 t o 1.242 mu l/cm(2) per hour) after stimulation with forskolin (10 mu M ). Ouabain (0.1 mu M) in the basolateral but not in the apical medium inhibited fluid secretion. Forskolin increased the intracellular cycli c AMP content of ADPKD and MDCK monolayers by 236 and 196%, respective ly. Six ADPKD monolayers had stable lumen negative transepithelial ele ctrical potential differences (PDte) of -1.4+/-0.3 mV, positive short circuit currents (SCC) of 11.9+/-2.1 mu Amp/cm(2) and a tissue resista nce (R(te)) of 116+/-14 ohm.cm(2). Forskolin increased SCC to 15.5+/-1 .9 mu Amp/cm(2) (P < 0.005) and decreased R(te) to 95+/-13 ohm.cm(2) ( P < 0.05); PDte remained stable at -1.4+/-0.3 mV. Ouabain (10 mu M) ha d no effect when added to the apical medium, but in the basolateral me dium decreased SCC to 1.7+/-0.3 mu Amp/cm(2) and PDte to -0.2+/-0.1 mV . We conclude that ADPKD cells in surface cysts have the potential to absorb or to secrete solutes and fluid, cAMP-mediated fluid secretion from the basolateral medium into the lumen of surface ADPKD cysts may be driven by anion transport.