Differential effects of brefeldin A on hormonally regulated Na + transport in a model renal epithelial cell line

Abstract

Na + transport in renal epithelia is regulated by a wide variety of endogenous and exogenous cellular factors. Although most natriferic agents have an action on the amiloride-sensitive Na + channel, the biochemical pathways which precede activation of the channel remain incompletely defined. One approach to dissecting such intricate pathways is to perturb a specific cellular process and determine its importance in the postulated mechanism. The current studies examine the effect of brefeldin A (BFA), an inhibitor of the central vacuolar system, on basal as well as aldosterone-, insulin-, and forskolin-stimulated Na + transport. In the A6 cell line, BFA had a time-dependent effect on basal transport. Aldosterone-induced Na + transport was sensitive to BFA while insulin's action was only partially blocked and forskolin-stimulated Na + transport was relatively resistant to the action of the inhibitor. These studies highlight differences as well as points of convergence in the natriferic pathways.