Direct micropuncture evidence that matrix extracellular phosphoglycoprotein inhibits proximal tubular phosphate reabsorption

Abstract

Matrix extracellular phosphoglycoprotein (MEPE) is a putative phosphatonin that we have shown in previous studies to be phosphaturic in rats. Its site of action in the nephron remains to be confirmed. We made micropuncture collections from late proximal convoluted tubules in anaesthetized rats to assess directly the effect of MEPE on phosphate reabsorption in the proximal tubule. MEPE had no effect on glomerular filtration rate or single-nephron filtration rate, but it increased phosphate excretion significantly. In animals infused with vehicle alone (time controls), no significant change was seen in either the proximal tubular fluid:plasma phosphate concentration ratio (TF/P(Pi)) or the fraction of filtered phosphate reaching the late proximal convoluted tubule (FD(Pi)); whereas in rats infused with MEPE, TF/P(Pi) increased from 0.49 ± 0.07 to 0.68 ± 0.04 (n = 22; P = 0.01) and FD(Pi) increased from 0.20 ± 0.03 to 0.33 ± 0.03 (n = 22; P < 0.01). The results confirm the phosphaturic effect of MEPE and indicate that much, if not all, of this effect is a result of reduced reabsorption of phosphate in the proximal convoluted tubule. This is consistent with the recent finding of MEPE-induced reductions in apically located NaPT2a in the proximal tubule.