SITE AND MECHANISM OF ACTION OF EPIDERMAL GROWTH-FACTOR IN RABBIT CORTICAL COLLECTING DUCT

To examine the exact target cell and mechanism of action of epidermal growth factor (EGF) in the isolated cortical collecting duct from rabbit kidney, we compared electrical properties of collecting duct (CD) cells (principal cells) and intercalated (IC) cells in absence and presence of EGF at 10(-8) M. Differentiation of CD and IC cells was based on values of basolateral membrane voltage (V(b)) and fractional apical membrane resistance (fR(a)). In CD cells, upon addition of EGF to bath, lumen-negative transepithelial voltage (V(T)) was decreased from -8.0 +/- 1.9 to -2.4 +/- 1.3 mV (n = 22, P < 0.001), but V(b) was little changed (from -85.1 +/- 2.8 to -83.1 +/- 2.7 mV, n = 19), indicating that EGF in bath mainly caused changes in apical membrane voltage. In addition, peritubular EGF increased transepithelial resistance (R(T)) from 132.9 +/- 15.8 to 153.8 +/- 18.4-OMEGA.cm2 (n = 16, P < 0.001) as well as fR(a) from 0.31 +/- 0.06 to 0.39 +/- 0.07 (n = 12, P < 0.01). These actions of EGF were prevented by pretreatment with 50-mu-M luminal amiloride. Luminal EGF had no effects on V(T), V(b), R(T), or fR(a) of CD cells. In IC cells, upon addition of EGF to bath, neither V(b) nor fR(a) was affected. From these results, we conclude that EGF acts on the CD cell at the basolateral border and inhibits mainly the amiloride-sensitive Na+ conductance in the apical membrane.