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 |
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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 ; BARON, R</creator><creatorcontrib>MUNMUN CHAKRABORTY ; DIPTENDU CHATTERJEE ; GORELICK, F. S ; BARON, R</creatorcontrib><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><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.91.6.2115</identifier><identifier>PMID: 8134357</identifier><identifier>CODEN: PNASA6</identifier><language>eng</language><publisher>Washington, DC: National Acad Sciences</publisher><subject>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</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1994-03, Vol.91 (6), p.2115-2119</ispartof><rights>1994 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c465t-17249df67c551ca13cb1280c4ea99ec7357f2cc4128c783ef01fcf8585a9a783</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/91/6.cover.gif</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC43320/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC43320/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=4114474$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8134357$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>MUNMUN CHAKRABORTY</creatorcontrib><creatorcontrib>DIPTENDU CHATTERJEE</creatorcontrib><creatorcontrib>GORELICK, F. 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. Psychology</subject><subject>Kidney Tubules, Proximal - cytology</subject><subject>Kidney Tubules, Proximal - enzymology</subject><subject>Kidney Tubules, Proximal - metabolism</subject><subject>Ouabain - pharmacology</subject><subject>Rats</subject><subject>Signal Transduction</subject><subject>Sodium-Hydrogen Exchangers - metabolism</subject><subject>Sodium-Potassium-Exchanging ATPase - metabolism</subject><subject>Vertebrates: urinary system</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1994</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UUtvEzEQthCohMKVG5IPqCc2tXe9L4lLFQFFjUoPuVuT2XFi6niX9W7V_A1-Md42ROHCydL3mhl_jL2XYi5FmV12HsK8lvNinkqZv2AzKWqZFKoWL9lMiLRMKpWq1-xNCD-FEHVeiTN2VslMZXk5Y78X5BzHPTpKGurIN-QHDr7h9zYmUxI6Qmss8p42o4PBtp63hg9b4tBZBMdv4fKa0yNuwW-of_JO7C18ukmuVncxhFv_BN3bxtOe4zTSWU98uVwkdzeSryMIDu3QeuvfslcGXKB3h_ecrb5-WS2uk-WPb98XV8sEVZEPiSxTVTemKDHPJYLMcC3TSqAiqGvCMp5nUkQVQSyrjIyQBk2VVznUEIFz9vk5thvXO2ow3t2D011vd9DvdQtW_8t4u9Wb9kGrLEtFtF8c7H37a6Qw6J0N02XgqR2DLgslilhDFM6fhdi3IfRkjiOk0FOFeqpQ11IXeqowGj6cLnaUHzqL_McDDyH-munBow1HmZJSqVKdxEzxf9nTMRf_47UZnRvoccj-AFcnvRA</recordid><startdate>19940315</startdate><enddate>19940315</enddate><creator>MUNMUN CHAKRABORTY</creator><creator>DIPTENDU CHATTERJEE</creator><creator>GORELICK, F. S</creator><creator>BARON, R</creator><general>National Acad Sciences</general><general>National Academy of Sciences of the United States of America</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19940315</creationdate><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><author>MUNMUN CHAKRABORTY ; DIPTENDU CHATTERJEE ; GORELICK, F. S ; BARON, R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c465t-17249df67c551ca13cb1280c4ea99ec7357f2cc4128c783ef01fcf8585a9a783</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1994</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Calcitonin - pharmacology</topic><topic>Calcium-Calmodulin-Dependent Protein Kinase Type 2</topic><topic>Calcium-Calmodulin-Dependent Protein Kinases - metabolism</topic><topic>Cell Cycle</topic><topic>Cell Line</topic><topic>Fundamental and applied biological sciences. 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. S</creatorcontrib><creatorcontrib>BARON, R</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>MUNMUN CHAKRABORTY</au><au>DIPTENDU CHATTERJEE</au><au>GORELICK, F. S</au><au>BARON, R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>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</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>1994-03-15</date><risdate>1994</risdate><volume>91</volume><issue>6</issue><spage>2115</spage><epage>2119</epage><pages>2115-2119</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><coden>PNASA6</coden><abstract>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.</abstract><cop>Washington, DC</cop><pub>National Acad Sciences</pub><pmid>8134357</pmid><doi>10.1073/pnas.91.6.2115</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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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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