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Am J Physiol Renal Physiol 276: F72-F78, 1999;
0363-6127/99 $5.00
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Vol. 276, Issue 1, F72-F78, January 1999

Epidermal growth factor inhibits Na-Pi cotransport in weaned and suckling rats

Mazen Arar1, Hubert K. Zajicek2, Ihsan Elshihabi1
Moshe Levi2
(With the Technical Assistance of Myrna Gonzales and Paul Wilson)

1 Department of Pediatrics, University of Texas Health Science Center at San Antonio, San Antonio 78284; and 2 Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas and Veterans Affairs Medical Center, Dallas, Texas 75216

In the present study, we determined the effect of epidermal growth factor (EGF; 10 µg/100 g body wt) on sodium gradient-dependent phosphate transport (Na-Pi cotransport) regulation in suckling (12-day-old) and weaned (24-day-old) rats. Weaned rats had higher proximal tubular brush border membrane vesicle (BBMV) Na-Pi cotransport activity (232 ± 16 in weaned vs. 130 ± 9 pmol · 10 s-1 · mg protein-1 in suckling rats, P < 0.05). Chronic treatment with EGF induced inhibition of BBMV Na-Pi cotransport in both suckling (130 ± 9 vs. 104 ± 7 pmol · 10 s-1 · mg protein-1, P < 0.05) and weaned rats (232 ± 16 vs. 145 ± 9 pmol · 10 s-1 · mg protein-1, P < 0.005). The inhibitory effect was selective for Na-Pi cotransport as there was no inhibition of Na-glucose cotransport. Weaned rats had a higher abundance of BBMV NaPi-2 protein than suckling rats (increase of 54%, P < 0.001) and a twofold increase in NaPi-2 mRNA. The EGF-induced inhibition of Na-Pi transport was paralleled by decreases in NaPi-2 protein abundance in both weaned (decrease of 26%, P < 0.01) and suckling (decrease of 27%, P < 0.01) animals. In contrast, there were no changes in NaPi-2 mRNA abundance. We conclude that proximal tubule BBMV Na-Pi cotransport activity, NaPi-2 protein abundance, and NaPi-2 mRNA abundance are higher in weaned than in suckling rats. EGF inhibits Na-Pi cotransport activity in BBMV isolated from suckling and weaned rats, and this inhibition is mediated via a decrease in NaPi-2 protein abundance, in the absence of a change in NaPi-2 mRNA.

NaPi-2 mRNA; NaPi-2 protein; phosphate transporter maturation


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