| Autor: |
Yue G; Center for Cell and Molecular Signaling, Emory University School of Medicine, Atlanta, Georgia 30322, USA., Edinger RS, Bao HF, Johnson JP, Eaton DC |
| Jazyk: |
angličtina |
| Zdroj: |
American journal of physiology. Cell physiology [Am J Physiol Cell Physiol] 2000 Jul; Vol. 279 (1), pp. C81-8. |
| DOI: |
10.1152/ajpcell.2000.279.1.C81 |
| Abstrakt: |
Rapamycin and FK-506 are immunosuppressive drugs that bind a ubiquitous immunophilin, FKBP12, but immunosuppressive mechanisms and side effects appear to be different. Rapamycin binds renal FKBP12 to change renal transport. We used cell-attached patch clamp to examine rapamycin's effect on Na(+) channels in A6 cells. Channel NP(o) was 0.5 +/- 0.08 (n = 6) during the first 5 min but fell close to zero after 20 min. Application of 1 microM rapamycin reactivated Na(+) channels (NP(o) = 0.47 +/- 0.1; n=6), but 1 microM FK-506 did not. Also, GF-109203X, a protein kinase C (PKC) inhibitor, mimicked the rapamycin-induced reactivation in a nonadditive manner. However, rapamycin did not reactivate Na(+) channels if cells were exposed to 1 microM FK-506 before rapamycin. In PKC assays, rapamycin was as effective as the PKC inhibitor; however, epithelial Na(+) channel (ENaC) phosphorylation was low under baseline conditions and was not altered by PKC inhibitors or activators. These results suggest that rapamycin activates Na(+) channels by binding FKBP12 and inhibiting PKC, and, in renal cells, despite binding the same immunophilin, rapamycin and FK-506 activate different intracellular signaling pathways. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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