Effect of epidermal growth factor on sodium transport in the cortical collecting tubule

Abstract
Receptors for epidermal growth factor (EGF) have been demonstrated in the distal tubule. To determine whether there are acute functional correlates, we studied the effect of EGF on cortical collecting tubule (CCT) transepithelial voltage and transport of sodium and bicarbonate. Rabbit CCT were perfused in vitro and EGF was added to either the bathing medium or the luminal perfusate after base-line measurements of transport. Peritubular EGF in concentrations of 0.1 to 100 ng/ml (1.7 X 10(-11) to 1.7 X 10(-8) M) decreased sodium reabsorption, measured as 22Na absorption from the lumen, by 44-59%. There was a corresponding fall in the lumen-negative transepithelial voltage. Lower doses of EGF were without effect on transepithelial voltage or sodium transport. Pretreatment of the tubules with ouabain eliminated the effect of EGF on sodium transport. In contrast to peritubular EGF, luminal EGF (100 ng/ml) did not affect sodium transport. Peritubular EGF had no effect on either bicarbonate secretion or net bicarbonate transport in the CCT and no effect on net bicarbonate reabsorption in the medullary collecting tubule. Using the pH sensitive, fluorescent dye 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein, no change in principal cell intracellular pH was found after peritubular EGF. Two other growth factors, insulin and insulin-like growth factor I were without effect on sodium transport. We conclude that EGF inhibits active sodium absorption in CCT via receptors located at the basolateral membrane.