DEPRIVATION OF PHOSPHATE INCREASES IGF-II MESSENGER-RNA IN MDCK CELLSBUT IGFS ARE NOT INVOLVED IN PHOSPHATE-TRANSPORT ADAPTATION TO PHOSPHATE DEPRIVATION

Phosphate (Pi) deprivation and IGFs stimulate renal Pi reabsorption. W e studied the involvement of IGFs in the adaptation of Pi transport to Pi deprivation in MDCK cells. Deprivation of Pi for 15 h increased th e steady-state content of IGF-II mRNA (77 +/- 12%) whereas IGF-I mRNA was not detectable in MDCK cells in either control or Pi-deprived cell s. IGF-II (10(-7) M) and IGF-I (10(-8) M) stimulated the Na-dependent Pi uptake (1.23- and 1.3-fold increase at 15 h respectively). The effe ct of IGF-T appeared after 15 h and increased up to 40 h of treatment (2.15-fold increase). In contrast, Pi uptake was increased by Pi depri vation as early as 8 h (1.5-fold) and up to 40 h of Pi deprivation (1. 9-fold increase). IGF-II mRNA was not increased before 15 h of Pi depr ivation and returned to control at 40 h. The combination of IGF-I and Pi deprivation had a more than additive effect on Pi transport (fivefo ld increase) (P<0.001). At variance with Pi deprivation, high concentr ations of insulin stimulated Na-coupled alanine transport (6 +/- 2% an d 16 +/- 4% in Pi-treated and Pi-depleted cells respectively). Pi depr ivation and high concentrations of insulin decreased Na,K-ATPase activ ity (-48 and -64% respectively) and these effects were not additive. W e concluded that: (1) long-term Pi deprivation increased the content o f IGF-II mRNA in MDCK cells but that the paracrine/autocrine effects o f IGFs could not account for the effects of Pi deprivation on Pi trans port in MDCK cells and (2) IGFs could be involved in other changes occ urring during Pi deprivation such as the decrease in Na,K-ATPase activ ity.