Cell cycle-dependent and kinase-specific regulation of the apical Na/H exchanger and the Na,K-ATPase in the kidney cell line LLC-PK1 by calcitonin

Calcitonin (CT), which regulates serum calcium through its actions in bone and the kidney tubule, also has a potent natriuretic effect in vivo. Na reabsorption in the proximal kidney tubule is mostly dependent on the activity of the Na,K-ATPase and the apical Na/H exchanger. We have previously shown...

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Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS 1994-03, Vol.91 (6), p.2115-2119
Hauptverfasser: MUNMUN CHAKRABORTY, DIPTENDU CHATTERJEE, GORELICK, F. S, BARON, R
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container_issue 6
container_start_page 2115
container_title Proceedings of the National Academy of Sciences - PNAS
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creator MUNMUN CHAKRABORTY
DIPTENDU CHATTERJEE
GORELICK, F. S
BARON, R
description Calcitonin (CT), which regulates serum calcium through its actions in bone and the kidney tubule, also has a potent natriuretic effect in vivo. Na reabsorption in the proximal kidney tubule is mostly dependent on the activity of the Na,K-ATPase and the apical Na/H exchanger. We have previously shown that CT regulates the activity of the Na,K-ATPase in the proximal kidney tubule cell line LLC-PK1 in a cell cycle-dependent manner. We report here that, in the same cells, CT also regulates the Na/H exchanger through a cell cycle-specific activation of the Ca/calmodulin-dependent protein kinase II. In G2 phase, no changes in ethylisopropyl amiloride-sensitive 22Na uptake is observed, despite an increase in cAMP. In contrast, the hormone inhibits the apical exchanger when the cells are in S phase, resulting in an 80% inhibition of 22Na uptake. These results demonstrate that CT affects the activity of the two major proximal tubule Na transport systems and may help clarify the mechanisms by which CT regulates Na+ reabsorption.
doi_str_mv 10.1073/pnas.91.6.2115
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S</creatorcontrib><creatorcontrib>BARON, R</creatorcontrib><title>Cell cycle-dependent and kinase-specific regulation of the apical Na/H exchanger and the Na,K-ATPase in the kidney cell line LLC-PK1 by calcitonin</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Calcitonin (CT), which regulates serum calcium through its actions in bone and the kidney tubule, also has a potent natriuretic effect in vivo. Na reabsorption in the proximal kidney tubule is mostly dependent on the activity of the Na,K-ATPase and the apical Na/H exchanger. We have previously shown that CT regulates the activity of the Na,K-ATPase in the proximal kidney tubule cell line LLC-PK1 in a cell cycle-dependent manner. We report here that, in the same cells, CT also regulates the Na/H exchanger through a cell cycle-specific activation of the Ca/calmodulin-dependent protein kinase II. In G2 phase, no changes in ethylisopropyl amiloride-sensitive 22Na uptake is observed, despite an increase in cAMP. In contrast, the hormone inhibits the apical exchanger when the cells are in S phase, resulting in an 80% inhibition of 22Na uptake. These results demonstrate that CT affects the activity of the two major proximal tubule Na transport systems and may help clarify the mechanisms by which CT regulates Na+ reabsorption.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Calcitonin - pharmacology</subject><subject>Calcium-Calmodulin-Dependent Protein Kinase Type 2</subject><subject>Calcium-Calmodulin-Dependent Protein Kinases - metabolism</subject><subject>Cell Cycle</subject><subject>Cell Line</subject><subject>Fundamental and applied biological sciences. 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Psychology</topic><topic>Kidney Tubules, Proximal - cytology</topic><topic>Kidney Tubules, Proximal - enzymology</topic><topic>Kidney Tubules, Proximal - metabolism</topic><topic>Ouabain - pharmacology</topic><topic>Rats</topic><topic>Signal Transduction</topic><topic>Sodium-Hydrogen Exchangers - metabolism</topic><topic>Sodium-Potassium-Exchanging ATPase - metabolism</topic><topic>Vertebrates: urinary system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>MUNMUN CHAKRABORTY</creatorcontrib><creatorcontrib>DIPTENDU CHATTERJEE</creatorcontrib><creatorcontrib>GORELICK, F. 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source Jstor Complete Legacy; MEDLINE; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry
subjects Animals
Biological and medical sciences
Calcitonin - pharmacology
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calcium-Calmodulin-Dependent Protein Kinases - metabolism
Cell Cycle
Cell Line
Fundamental and applied biological sciences. Psychology
Kidney Tubules, Proximal - cytology
Kidney Tubules, Proximal - enzymology
Kidney Tubules, Proximal - metabolism
Ouabain - pharmacology
Rats
Signal Transduction
Sodium-Hydrogen Exchangers - metabolism
Sodium-Potassium-Exchanging ATPase - metabolism
Vertebrates: urinary system
title Cell cycle-dependent and kinase-specific regulation of the apical Na/H exchanger and the Na,K-ATPase in the kidney cell line LLC-PK1 by calcitonin
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