Fk506 and rapamycin but not cyclosporin inhibit aldosterone
stimulated sodium transport in a6 cells.
Rokaw, Michael D., Michael E. West, Paul M. Palevsky, and John P.
Johnson.
Laboratory of Epithelial Cell Biology, Renal-Electrolyte Division,
University of Pittsburgh Medical Center and Medical Service, Oakland
VA Medical Center, Pittsburgh, PA
APStracts 3:0046C, 1996.
The immunosuppressants cyclosporin A (CYA) and FK506 and
Rapamycin(RAP) have multiple actions on target cells which appear to
be mediated by interaction of drug-binding protein complexes. Both
FK506 and CYA, but not RAP inhibit the calcium-dependent phosphatase,
calcineurin and in so doing have been found to inhibit Na+/K+-ATPase
activity in various nephron segments. Of interest, FK506 and RAP, but
not CYA, are bound by the steroid receptor-associated FK506-binding
protein-heat shock protein, hsp56. To determine the physiologic
effect of this interaction on a steroid mediated phenomenon, the
effect of these agents on steroid-mediated sodium transport in A6
cells was investigated. Aldosterone stimulation of sodium transport,
and Na+/K+-ATPase activity is significantly inhibited by prolonged
incubation with FK506 and RAP. Although CYA inhibits basal Na+/K+
-ATPase activity, it has no effect on aldosterone induced Na+
transport or the aldosterone induced increase in Na+/K+-ATPase
activity. FK506 inhibits the aldosterone-induced synthesis of G
[alpha]I3 but has no effect on glucocorticoid receptor number as
quantified by Western Blotting. The results suggest that FK506 and
RAP inhibit steroid mediated sodium transport at some pre
-translational site. The common interaction of these agents with the
steroid receptor associated hsp56 might account for these findings.
Received 29 August 1995; accepted in final form 9 Janury 1996.
APS Manuscript Number C531-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 February 96