Document Detail


Effect of cyclosporine A on Na+/K(+)-ATPase, Na+/K+/2Cl- cotransporter, and H+/K(+)-ATPase in MDCK cells and two subtypes, C7 and C11.
MedLine Citation:
PMID:  9438176     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We investigated the influence of cyclosporine A (CsA) on key plasma membrane ion transport systems Na+/K(+)-ATPase, Na+/K+/2Cl- cotransporter, and H+/K(+)-ATPase in MDCK cells and two subtypes, C7 and C11, serving as a model system to study principal (C7) and intercalated (C11) cell properties of the distal nephron. The transport activity of Na+/K(+)-ATPase was significantly decreased in all cell types on CsA administration (8 x 10(-6) M) for 2 days, whereas the protein levels of Na+/K(+)-ATPase alpha-subunit in plasma membranes isolated from MDCK, C7, and C11 cells remained unchanged. The transport activity of Na+/K+/2Cl- cotransporter was significantly inhibited by CsA only in MDCK and C11 cells, but again plasma membrane protein levels were not altered. In contrast, C7 cell plasma membranes showed an increase of transport protein content, although the Na+/K+/2Cl- cotransporter activity was not affected by CsA. The H+/K(+)-ATPase transport activity remained unchanged in all three cell types. These data indicate that in C7 cells CsA might induce insertion of transporters into the plasma membrane, thus compensating the decrease of transport activity observed in MDCK and C11 cells. Furthermore, CsA significantly inhibited cell proliferation at 4 x 10(-6) M for C7 and C11 cells and at 8 x 10(-6) M for MDCK cells. Proliferation was completely abolished at 1.6 x 10(-5) M CsA. After 48 h of CsA incubation, the intracellular sodium concentration increased in all three different cell types; however, it stayed within the physiological range of mammalian cells. We, therefore, suggest that CsA is capable of reducing Na+/K(+)-ATPase and Na+/K+/2Cl- cotransporter activities in cells of the distal nephron, thereby contributing to the hyperkalemia observed in patients treated with CsA.
Authors:
C E Deppe; P J Heering; H Tinel; E Kinne-Saffran; B Grabensee; R K Kinne
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Experimental nephrology     Volume:  5     ISSN:  1018-7782     ISO Abbreviation:  Exp. Nephrol.     Publication Date:    1997 Nov-Dec
Date Detail:
Created Date:  1998-02-18     Completed Date:  1998-02-18     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  9302239     Medline TA:  Exp Nephrol     Country:  SWITZERLAND    
Other Details:
Languages:  eng     Pagination:  471-80     Citation Subset:  IM    
Affiliation:
Max-Planck-Institut für molekulare Physiologie, Abteilung Epithelphysiologie, Dortmund.
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MeSH Terms
Descriptor/Qualifier:
Animals
Biological Transport / drug effects
Carrier Proteins / metabolism*
Cell Line
Cell Membrane / drug effects,  metabolism
Cell Survival / drug effects
Cyclosporine / pharmacology*
Dogs
H(+)-K(+)-Exchanging ATPase / metabolism*
Immunosuppressive Agents / pharmacology*
Kidney / drug effects*,  metabolism
Sodium-Potassium-Chloride Symporters
Sodium-Potassium-Exchanging ATPase / metabolism*
Chemical
Reg. No./Substance:
0/Carrier Proteins; 0/Immunosuppressive Agents; 0/Sodium-Potassium-Chloride Symporters; 59865-13-3/Cyclosporine; EC 3.6.1.10/H(+)-K(+)-Exchanging ATPase; EC 3.6.3.9/Sodium-Potassium-Exchanging ATPase

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