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 (Ipi). Results. As a result, Ipi was observed in NaPi-IIa-expressing but not in H2O-injected Xenopus oocytes. Co-expression of mTOR significantly enhanced Ipi 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 g/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. © The Author 2010. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.