期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 275, 期 41, 页码 31601-31608出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M000600200
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资金
- NIDDK NIH HHS [DK-54396, T32 DK07257-17, DK-48482] Funding Source: Medline
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.
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