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 net transepithelial movement of liquid in response to
forskolin in isolated, intact
cysts excised from the surface of human
ADPKD kidneys and in cultured, polarized monolayers of epithelial cells derived from
ADPKD cysts. 10 excised
cysts bathed symmetrically in control culture medium secreted fluid at a rate of 0.19 +/- 0.03 microliter/cm2 per hour after stimulation with
forskolin (10 microM).
Ouabain (100 microM) addition to the cavity fluid did not change the rate of fluid secretion of 10
forskolin-treated
cysts, but addition of the
glycoside to the external bathing medium fluid of nine
cysts decreased secretion to -0.004 +/- 0.05 microliter/cm2 per hour. 24 monolayers absorbed fluid (range -0.029 to -0.412 microliter/cm2 per hour); by contrast, fluid was secreted (range 0.074 to 1.242 microliters/cm2 per hour) after stimulation with
forskolin (10 microM).
Ouabain (0.1 microM) in the basolateral but not in the apical medium inhibited fluid secretion.
Forskolin increased the intracellular
cyclic AMP content of
ADPKD and MDCK monolayers by 236 and 196%, respectively. Six
ADPKD monolayers had stable lumen negative transepithelial electrical potential differences (PDte) of -1.4 +/- 0.3 mV, positive short circuit currents (SCC) of 11.9 +/- 2.1 microAmp/cm2 and a tissue resistance (Rte) of 116 +/- 14 ohm.cm2.
Forskolin increased SCC to 15.5 +/- 1.9 microAmp/cm2 (P < 0.005) and decreased Rte to 95 +/- 13 ohm.cm2 (P < 0.05); PDte remained stable at -1.4 +/- 0.3 mV.
Ouabain (10 microM) had no effect when added to the apical medium, but in the basolateral medium decreased SCC to 1.7 +/- 0.3 microAmp/cm2 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.