| Abstrakt: |
Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) activators, including rosiglitazone, reportedly affect fluid and electrolyte transport across a variety of epithelia. However, the transporters affected, including the cystic fibrosis anion channel (CFTR) and the epithelial Na+channel (ENaC), and the effects on net flux appear to be cell type or tissue specific. The goal of the current project was to determine the effects of chronic (2-4 day) rosiglitazone exposure on epithelial cells isolated from adult pig vas deferens, a tissue known to express CFTR and to express ENaC when exposed to glucocorticoids. Results showed that, in the absence of glucocorticoids, rosiglitazone had little effect on electrophysiological parameters including baseline short circuit current, baseline transepithelial electrical resistance, and the responses to amiloride (an ENaC blocker) forskolin (an activator of adenyll cyclace), and DASU-02, a CFTR channel blocker. However, when cells were cultured in the presence of dexamethasone, rosiglitazone was associated with a 2-fold increase in baseline short circuit current and a two-fold increase in the magnitude of the amiloride-inhibitable short circuit current. These results suggest that PPAR-gamma activation in vas deferens epithelial cells causes a profound increase in Na+absorption that would likely change the luminal environment and reduce the luminal volume in the vas deferens, effects that would likely affect sperm viability or function. [Supported by NIH R01 HD058398](poster) |
