poster abstractPolycystic kidney disease (PKD) is a genetic disease that causes the formation of fluid-filled cysts
in the kidney and other organs such as the liver and pancreas. Kidney function is seemingly
unaltered despite substantial cyst development over the first four to six decades of life, but then
the decline in renal function is precipitous often leading to complete renal failure in 5 years.
Antidiuretic hormone (ADH) causes an increase in Cl- secretion into the cyst lumen, and one of
the drugs in human clinical trials for treatment of PKD is an ADH receptor antagonist. The
hormone works by stimulating cAMP production, which leads to the Cl- secretion. Interestingly,
we have found that cyst fluid from human patients also causes a secretory Cl- flux that can lead to
the growth of the remaining intact cysts. The active component of the cyst fluid is LPA, a
phospholipid that acts as an extracellular signaling molecule. This secretion is important in late
stage disease when large cysts are likely to leak or burst contributing to the rapid decline in renal
function. Electrophysiological techniques were implemented to compare the ion fluxes stimulated
by ADH and LPA. In the mpkCCDc14 (mouse principal cells of the cortical collecting duct clone
4) cell line we found that the Cl- secretory pathways stimulated by the two factors are separate
and independent. Further indication of this separation is our finding that LPA stimulation does
not increase cAMP levels. Therefore we have identified an additional target for potential
pharmaceutical intervention in the treatment of PKD
