Peptide growth factors play important roles in renal function, disease response and development. In particular, EGF has many effects in the kidney. We have recently shown that EGF has a specific effect on PCT transport to stimulate phosphate transport (Quigley, R and M. Baum, 1991, Epidermal growth factor (EGF) stimulates phosphate transport (J-phos) in the rabbit proximal convoluted tubule (PCT), J. Am. Soc,. Nephrol. 2:444A). TGFalpha binds to the EGF receptor to elicit its effects and should therefore have similar effects to EGF. In the PCT, however, TGFalpha stimulated phosphate transport at a concentration that was one-hundredth that of EGF. In addition, TGFalpha also stimulated volume absorption, glucose transport and bicarbonate transport. The current proposal is designed to examine these differential effects of EGF and TGFalpha in the PCT.
The aims of this proposal are: 1) further define the differences in the effects of EGF and TGFalpha on PCT solute transport, 2) examine the binding of EGF and TGFalpha to the PCT to determine if there are separate binding sites, 3) examine the second messenger systems employed by EGF and TGFalpha in intracellular signalling in the PCT, and 4) determine the metabolic processing of the ligand-receptor complex of EGF and TGFalpha in renal tissue. The techniques employed in this proposal include in vitro microperfusion of PCT, binding studies, primary cell culture, immunoblots of phosphotyrosine proteins, measurements of Ip3, DAG and intracellular calcium, and pulse-chase experiments.
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