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1 Department of Physiology and Biophysics and 2 Division of Nephrology, Department of Medicine, University of Southern California Keck School of Medicine, Los Angeles, California 90089-9142
Renal cortical phenol injection provokes
acute sympathetic nervous system-dependent hypertension and a shift of
proximal tubule Na+/H+ exchanger isoform 3 (NHE3) and Na+-Pi cotransporter type 2 (NaPi2)
to apical microvilli. This study aimed to determine whether proximal
tubule (PT) Na+ transporter redistribution persists
chronically and whether the pool sizes of renal Na+
transporters are altered. At 5 wk after a 50-µl 10% phenol
injection, blood pressure is elevated: 154 ± 8 vs. 113 ± 11 mmHg after saline injection. Cortical membranes were fractionated into
three "windows" enriched in apical brush border (WI),
mixed apical and intermicrovillar cleft (WII), and
intracellular membranes (WIII). NHE3 relative distribution
in these windows, assessed by immunoblots and expressed as %total,
remained shifted to apical from intracellular membranes (WI:
25.3 ± 3 in phenol vs.12.7 ± 3% in saline and
WIII: 9.1 ± 1.3 in phenol vs. 18.9 ± 3% in
saline). NaPi2 and dipeptidyl-peptidase IV also remained shifted to
WI, and alkaline phosphatase activity increased 100.9 ± 29.7 (WI) and 51.4 ± 17.5% (WII) in
phenol-injected membranes. Na+ transporter total abundance
[NHE3, NaPi2, thiazide-sensitive Na-Cl cotransporter,
bumetanide-sensitive Na-K-2Cl cotransporter, Na-K-ATPase
1- and
1-subunits, and epithelial
Na+ channel (ENaC)
- and
-subunits] was profiled by
immunoblotting. Only cortical NHE3 abundance was altered, decreasing to
0.56 ± 0.06. The results demonstrate that phenol injury provokes
a persistant shift of PT NHE3 and NaPi2 to the apical microvilli, along
with a 44% decrease in total NHE3, evidence for an escape mechanism that would counteract the redistribution of a larger fraction of NHE3
to the apical surface by normalizing the total amount of NHE3 in apical membranes.
sodium transport; membrane traffic; sympathetic nervous system; phenol
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