Suppression of CFTR-mediated Cl(-) secretion by enhanced expression of epithelial Na(+) channels in mouse endometrial epithelium.

The present study investigated the effect of enhanced expression of epithelial Na(+) channels (ENaC) on the cystic fibrosis transmembrane conductance regulator (CFTR)-mediated Cl(-) secretion in the mouse endometrium using the short-circuit current technique. The amiloride sensitivity of the basal current of the cultured endometrial epithelia was found to vary with the magnitude of the basal current, the higher the basal current the greater its sensitivity to amiloride, indicating possible elevation of ENaC expression. However, the magnitude of the forskolin-induced Isc, previously demonstrated to be mediated by CFTR, decreased as the amiloride sensitivity of the basal current increased, suggesting a possible inhibitory effect of elevated expression of ENaC on CFTR-mediated Cl(-) secretion. The Matrigel concentration for culturing the endometrial epithelia was found to affect the amiloride sensitivity of the basal current as well as the forskolin-induced Isc in opposite directions. However, competitive RT-PCR demonstrated that the expression of both ENaC and CFTR was enhanced in Matrigel-treated culture, suggesting that the reduced forskolin-induced Isc with enhanced amiloride sensitivity was not due to a reduction in CFTR expression, but rather suppression of CFTR function by enhanced ENaC expression. In addition to the previously demonstrated inhibition of ENaC by activation of CFTR, the present results reveal possible regulation of CFTR by ENaC. The interaction between the two may be one of the underlying mechanisms for balancing Na(+) absorption and Cl(-) secretion across epithelia. Copyright 2000 Academic Press.