Rapamycin-induced phosphaturia.

Abstract

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.

• Authors: Daniela S Kempe, Miribane Dërmaku-Sopjani, Henning Fröhlich, Mentor Sopjani, Anja Umbach, Goverdhan Puchchakayala, Anna Capasso, Florian Weiss, Michael Stübs, Michael Föller, Florian Lang
• Journal: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association (Nephrol Dial Transplant) Vol. 25 Issue 9 Pg. 2938-44 (Sep 2010) ISSN: 1460-2385 [Electronic] England
• PMID: 20368307 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Immunosuppressive Agents
• Phosphates
• Sodium-Phosphate Cotransporter Proteins, Type IIa
• mTOR protein, rat
• TOR Serine-Threonine Kinases
• Sirolimus

Topics

• Animals
• Biological Transport
• Female
• Hypophosphatemia, Familial (chemically induced, metabolism)
• Immunoenzyme Techniques
• Immunosuppressive Agents (toxicity)
• Kidney (drug effects, metabolism)
• Male
• Mice
• Oocytes (cytology, drug effects, metabolism)
• Phosphates (urine)
• Rats
• Sirolimus (toxicity)
• Sodium-Phosphate Cotransporter Proteins, Type IIa (metabolism)
• TOR Serine-Threonine Kinases (genetics, metabolism)
• Xenopus laevis