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 ultrafiltrateLike 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 (J(Phos)) in a dose-dependent fashion but did not affect volume absorption (J(v)) or bicarbonate transport (J(tCo2).) At 3 x 10(-7) M, EGF stimulated PCT J(v) and J(tCo2), in addition to the stimulation in J(Phos) TGF-alpha stimulated J(v), J(tCo2), and J(Phos), 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 J(tCo2), and at 3 x 10(-12) M, TGF-alpha also stimulated J(v) and J(Phos). 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 J(v) and J(tCo2). Neither luminzl EGF nor TGF-alpha had an effect on PCT transport. PCT bicarbon.ate 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.