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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Clinical Investigator Award (CIA) (K08)
Project #
1K08DK002232-01
Application #
3081132
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Project Start
1993-08-01
Project End
1998-07-31
Budget Start
1993-08-01
Budget End
1994-07-31
Support Year
1
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Type
Schools of Medicine
DUNS #
City
Dallas
State
TX
Country
United States
Zip Code
75390
Quigley, Raymond; Mulder, Jaap; Baum, Michel (2003) Ontogeny of water transport in the rabbit proximal tubule. Pediatr Nephrol 18:1089-94
Quigley, R; Lisec, A; Baum, M (2001) Ontogeny of rabbit proximal tubule urea permeability. Am J Physiol Regul Integr Comp Physiol 280:R1713-8
Quigley, R; Baum, M; Reddy, K M et al. (2000) Effects of 20-HETE and 19(S)-HETE on rabbit proximal straight tubule volume transport. Am J Physiol Renal Physiol 278:F949-53
Quigley, R; Gupta, N; Lisec, A et al. (2000) Maturational changes in rabbit renal basolateral membrane vesicle osmotic water permeability. J Membr Biol 174:53-8
Quigley, R; Flynn, M; Baum, M (1999) Maturational changes in rabbit renal brush border membrane vesicle urea permeability. Pediatr Res 45:143-7
Quigley, R; Flynn, M; Baum, M (1999) Neonatal and adult rabbit renal brush border membrane vesicle solute reflection coefficients. Biol Neonate 76:106-13
Shah, M; Quigley, R; Baum, M (1999) Neonatal rabbit proximal tubule basolateral membrane Na+/H+ antiporter and Cl-/base exchange. Am J Physiol 276:R1792-7
Baum, M; Quigley, R (1998) Inhibition of proximal convoluted tubule transport by dopamine. Kidney Int 54:1593-600
Quigley, R; Harkins, E W; Thomas, P J et al. (1998) Maturational changes in rabbit renal brush border membrane vesicle osmotic water permeability. J Membr Biol 164:177-85
Shah, M; Quigley, R; Baum, M (1998) Maturation of rabbit proximal straight tubule chloride/base exchange. Am J Physiol 274:F883-8

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