Rapamycin-induced phosphaturia.
BACKGROUND
The mammalian target of rapamycin (mTOR) is known to stimulate a variety of transport mechanisms including the intestinal phosphate transporter NaPi-IIb. The present study was performed to elucidate whether mTOR similarly regulates the major renal tubular phosphate transporter NaPi-IIa.


METHODS
To this end, NaPi-IIa was expressed in Xenopus oocytes with or without mTOR and phosphate transport estimated from phosphate-induced (1 mM) current (I(pi)).


RESULTS
As a result, I(pi) was observed in NaPi-IIa-expressing but not in H(2)O-injected Xenopus oocytes. Co-expression of mTOR significantly enhanced I(pi) in NaPi-IIa-expressing Xenopus oocytes, an effect abrogated by treatment with rapamycin (50 nM for the last 24 h of incubation). In a second series of experiments, the effect of rapamycin was analysed in mice. The in vivo administration of rapamycin (3 microg/g body weight/day) for 3 days resulted in phosphaturia in mice despite a tendency of plasma phosphate concentration to decrease.


CONCLUSIONS
mTOR contributes to the regulation of renal phosphate transport, and rapamycin thus influences phosphate balance.
Kempe
Daniela S
DS
Department of Physiology, University of Tübingen, Gmelinstr. 5, D-72076, Tübingen, Germany.
Dërmaku-Sopjani
Miribane
M
Fröhlich
Henning
H
Sopjani
Mentor
M
Umbach
Anja
A
Puchchakayala
Goverdhan
G
Capasso
Anna
A
Weiss
Florian
F
Stübs
Michael
M
Föller
Michael
M
Lang
Florian
F
D000818:Animals; D001692:Biological Transport; D005260:Female; D007015:Hypophosphatemia, Familial / Q000139:chemically induced* / Q000378:metabolism; D007124:Immunoenzyme Techniques; D007166:Immunosuppressive Agents / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D009865:Oocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010710:Phosphates / Q000652:urine*; D051381:Rats; D020123:Sirolimus / Q000633:toxicity*; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis
D007166:Immunosuppressive Agents; D010710:Phosphates; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa; C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus