Cellular mechanisms of acute and chronic adaptation of rat renal P_i transporter to alterations in dietary P_i

Recently, the cDNA for a Na-P_i cotransport system of rat kidney cortex (NaPi-2) has been identified by expression cloning. Using polyclonal antibodies raised against this renal Na-P_i cotransport system, and using the polymerase chain reaction after reverse transcription of mRNA in microdissected nephron segments, we recently demonstrated that NaPi-2-related mRNA and protein is expressed in the brush-border membranes (BBM) of the proximal tubules of rat kidney. The purpose of the present study was to study the cellular mechanisms involved in adaptation of rat renal Na-P_i cotransporter to acute and chronic alterations in dietary P_i. Compared with rats fed chronically (7 days) a high-P_i diet (1.2%), in rats fed chronically a low-P_i (0.1%) diet the 3.4-fold increase in BBM Na-P_i cotransport rate (chronic upregulation) was associated with a 2.2-fold increase in renal cortical NaPi-2 mRNA and a 4.9-fold increase in BBM NaPi-2 protein abundances. In contrast, compared with rats fed chronically (7 day) a high-P_i diet, in rats fed acutely (2 h) a low-P_i diet the 1.5-fold increase in Na-P_i cotransport rate (acute upregulation) was associated with a 1.8-fold increase in NaPi-2 protein but no change in NaPi-2 mRNA abundance. Similarly, compared with rats fed chronically a low-P_i diet, in rats fed acutely (2 h) a high-P_i diet the 1.9-fold decrease in Na-P_i cotransport rate (acute downregulation) was associated with a 3.8-fold decrease in NaPi-2 protein but no change in NaPi-2 mRNA abundance. The results suggest that under chronic conditions protein synthesis is involved in the adaptive response to alterations in dietary P_i content. On the other hand, under acute conditions the number of Na-P_i cotransporters in the proximal tubular BBM can be rapidly changed by mechanisms independent of protein synthesis.