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J. Biol. Chem., Vol. 275, Issue 41, 31601-31608, October 13, 2000
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From the Medical Service, Department of Veterans Affairs Medical
Center and Department of Internal Medicine, University of Texas
Southwestern Medical Center, Dallas, Texas 75235
Parathyroid hormone (PTH) is a potent inhibitor
of mammalian renal proximal tubule Na+
transport via its action on the apical membrane
Na+/H+ exchanger NHE3. In the opossum kidney
cell line, inhibition of NHE3 activity was detected from 5 to 45 min after PTH addition. Increase in NHE3 phosphorylation on multiple
serines was evident after 5 min of PTH, but decrease in surface NHE3
antigen was not detectable until after 30 min of PTH. The decrease in
surface NHE3 antigen was due to increased NHE3 endocytosis. When
endocytic trafficking was arrested with a dominant negative dynamin
mutant (K44A), the early inhibition (5 min) of NHE3 activity by PTH was not affected, whereas the late inhibition (30 min) and decreased surface NHE3 antigen induced by PTH were abrogated. We conclude that
PTH acutely inhibits NHE3 activity in a biphasic fashion by NHE3
phosphorylation followed by dynamin-dependent endocytosis.
Acute Regulation of Na+/H+ Exchanger NHE3
by Parathyroid Hormone via NHE3 Phosphorylation and
Dynamin-dependent Endocytosis*
,
*
This work was supported in part by National Institutes of
Health Grants DK-48482 and DK-54396, the Department of Veterans Affairs
Research Service, the American Heart Association Texas Affiliate Grant
98G-052, and the National Kidney Foundation of Texas.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Recipient of National Institutes of Health Training Grant T32
DK07257-17.
§
To whom correspondence should be addressed: Dept. Of Internal
Medicine, University of Texas Southwestern Medical Center, 5323 Harry
Hines Blvd., Dallas, TX 75235-8856. Tel.: 214-648-3152; Fax:
214-648-2071; E-mail: orson.moe@vtsouthwestern.edu.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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