Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1995-1-18
pubmed:abstractText
We reported that cyclosporin A (CsA) inhibits Na+/K(+)-ATPase activity in specific segments of the rat nephron. In this study, we tested the hypothesis that cyclosporin A reduces Na+/K(+)-ATPase activity through inhibition of calcineurin. In T cells, cyclosporin A and FK506 bind to immunophilins and inhibit the phosphatase activity of calcineurin; Rapamycin and SDZ 220-384 also bind to immunophilins but do not change calcineurin activity. Na+/K(+)-ATPase activity was measured in microdissected rat proximal tubule (S2 subsegment), medullary thick ascending limb (mTAL), and cortical collecting duct (CCD). First we found that two inhibitors of calcineurin, pentafluorophenol (PFP, 100 mM) and peptide 412 (1 mM), significantly reduced Na+/K(+)-ATPase activity in the CCD by 78% and 70%, respectively. In CCDs, FK506 inhibited Na+/K(+)-ATPase activity by 61 to 85% at concentrations of 1.5 to 6 ng/ml, but not at 0.5 ng/ml. FK506 (6 ng/ml) inhibited Na+/K(+)-ATPase activity in mTALs by 56% but did not inhibit it in S2s or glomeruli. In contrast, Rapamycin (12.5 ng/ml) did not change Na+/K(+)-ATPase activity in CCDs or mTALs, but at a concentration of 12.5 micrograms/ml did block the inhibitory effect of FK506 (6 ng/ml) in both segments. SDZ 220-384 (600 ng/ml) did not change Na+/K(+)-ATPase activity in CCDs. Thus, in CCDs and mTALs: (1) FK506, like cyclosporin A, inhibits Na+/K(+)-ATPase activity; (2) Rapamycin and SDZ 220-384 do not inhibit Na+/K(+)-ATPase activity; and (3) Rapamycin prevents FK506-induced inhibition of Na+/K(+)-ATPase activity. These responses may be explained by a direct inhibition of calcineurin activity yielding lower Na+/K(+)-ATPase activity in CCDs and mTALs.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0085-2538
pubmed:author
pubmed:issnType
Print
pubmed:volume
46
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
647-52
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Evidence that the inhibition of Na+/K(+)-ATPase activity by FK506 involves calcineurin.
pubmed:affiliation
Department of Medicine, Emory University School of Medicine, Atlanta, Georgia.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.