Effects of epidermal growth factor and transforming growth factor-alpha on rabbit proximal tubule solute transport.

The present in vitro microperfusion study examined the direct effects of epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) on rabbit proximal convoluted tubule (PCT) solute transport. Tubules were perfused with an ultrafiltrate-like solution and bathed in an ultrafiltrate-like solution containing albumin. Albumin binding studies showed that both growth factors were highly protein bound with a free fraction of EGF of 0.31 +/- 0.04% and TGF-alpha of 1.08 +/- 0.15%. EGF at concentrations from 3 x 10(-11) M to 3 x 10(-8) M stimulated phosphate transport (JPhos) in a dose-dependent fashion but did not affect volume absorption (Jv) or bicarbonate transport (JtCO2). At 3 x 10(-7) M, EGF stimulated PCT Jv and JtCO2 in addition to the stimulation in JPhos. TGF-alpha stimulated Jv, JtCO2, and JPhos, but its effects were seen at a concentration that was 100-fold lower than that where EGF affected PCT transport. At 3 x 10(-13) M, TGF-alpha stimulated JtCO2, and at 3 x 10(-12) M, TGF-alpha also stimulated Jv and JPhos. EGF receptor downregulation with 3 x 10(-8) M EGF was able to block the effect of 3 x 10(-10) M TGF-alpha on Jv and JtCO2. Neither luminal EGF nor TGF-alpha had an effect on PCT transport. PCT bicarbonate and mannitol permeabilities were also not affected by either growth factor. These results demonstrate that EGF and TGF-alpha have direct effects on PCT solute transport.