136 Implications for renal pathophysiology It must be recognized that the FL-MDCK cell line suffers from the limitations of any cell culture system when attempting to apply these results to an understanding of normal renal physiology or pathophysiology. Furthermore, even the type-1 MDCK cells used in these studies are heterologous, and their origin cannot be ascribed definitively to any nephron segment. Nevertheless, the ability of ATP to inhibit ENaC-mediated Na+ absorption and stimulate Cl− secretion, as shown in these experiments with FL-MDCK cells and in similar epithelia [42, 43, 49], suggests a role for such signaling in the nephron. Significant amounts of ATP are released from epithelial cells originating from all regions of the nephron, and multiple P2Y and P2X receptors have been identified in all segments of the nephron [48]. Thus, changes in the luminal ATP concentration in the cortical CD and other aldosterone-sensitive segments of the distal nephron, in which ENaC mediates Na+ transport, may be a physiologic signal for diminished Na+ reabsorption. Also, Wilson et al. [19] demonstrated significant accumulation of ATP in cyst fluid obtained from patients with autosomal dominant polycystic kidney disease. Thus, based on our observations in MDCK cells, it seems reasonable to speculate that ATP might favor cyst enlargement and consequent exacerbation of polycystic disease by inhibiting Na+ reabsorption and stimulating Cl− secretion [19, 52]. Acknowlegdments This work was part of a dissertation submitted in partial fulfillment of the requirements for the Ph.D. degree awarded to Y. Xie by the School of Graduate Studies at the University of Alabama at Birmingham in December 2004. We are particularly grateful to Dr. Ryan G. Morris, who developed the retrovirally transfected cell line used in these studies. 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