期刊
NEPHROLOGY DIALYSIS TRANSPLANTATION
卷 25, 期 9, 页码 2938-2944出版社
OXFORD UNIV PRESS
DOI: 10.1093/ndt/gfq172
关键词
mTOR; NaPi-IIa; phosphate; PTH; 1,25(OH)(2)D-3
资金
- Deutsche Forschungsgemeinschaft [La 315/4-3, La 315/6-1]
Background. The mammalian target of rapamycin (mTOR) is known to stimulate a variety of transport mechanisms including the intestinal phosphate transporter NaPi-lib. 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 H2O-injected Xenopus oocytes. Co-expression of mTOR significantly enhanced 10 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 mu 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.
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