Epidermal growth factor inhibits Na-Pi cotransport in weaned and suckling rats.
In the present study, we determined the effect of epidermal growth factor (EGF; 10 microgram/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.
Arar
M
M
Department of Pediatrics, University of Texas Health Science Center at San Antonio, San Antonio 78284, Texas.
Zajicek
H K
HK
Elshihabi
I
I
Levi
M
M
D000818:Animals; D000833:Animals, Suckling / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D007672:Kidney Cortex / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000378:metabolism; D008871:Microvilli / Q000378:metabolism; D010710:Phosphates / Q000652:urine; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters; D014886:Weaning
D002352:Carrier Proteins; D010710:Phosphates; D012333:RNA, Messenger; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters; D004815:Epidermal Growth Factor