Rapamycin-induced phosphaturia

*These authors contributed equally and thus share first authorship. Background. Themammalian 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 phos-phate 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 (Ipi). Results. As a result, Ipi was observed inNaPi-IIa-expressing but not in H2O-injected Xenopus oocytes. Co-expression of mTOR significantly enhanced Ipi inNaPi-IIa-expressingXe-nopus oocytes, an effect abrogated by treatment with rapa-mycin (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 µg/g body weight/day) for 3 days resulted in phosphaturia in mice despite a tendency of plasma phosphate concentra-tion to decrease. Conclusions. mTOR contributes to the regulation of renal phosphate transport, and rapamycin thus influences phos-phate balance