New aspects of adaptation of rat renal Na-Pi cotransporter to alterations in dietary phosphate

Abstract

A major regulator of Na-Pi cotransport is changes in dietary Pi content. Dietary Pi restriction is associated with an adaptive increase of the overall proximal tubular capacity to reabsorb Pi [1—5]. Part of this phenomenon is independent of extrarenal factors such as parathyroid hormone, 1,25-dihydroxyvitamin D3, plasma calcium, or growth hormone [6]. The adaptive phenomenon also occurs in renal tubular cells grown in culture upon lowering of the culture media Pi content [7—9]. In response to the in viva or cell culture Pi restriction, the increase in apical brush border membrane (BBM) Na-Pi cotransport is mediated by an increase in the Vrm,x, while there are no changes in the affinities of the transporter for Pi or Na ions. Previous in vivo and cell culture studies indicated that adaptation to chronic Pi restriction can be abolished by inhibitors of transcription and protein synthesis [7, 8, 10]. However, it could not be determined whether the proteins involved in the adaptive response represent newly synthesized Na-Pi cotransporters or if other regulatory proteins are involved. Recently, the cDNA for a Na-Pi cotransport system of rat kidney cortex (type 11 Na-Pi transporter, or NaPi-2) has been identified by expression cloning [111. Using polyclonal antibodies raised against this renal Na-Pi 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 apical brush border membrane of the proximal tubules of rat kidney [121. These advances made it possible to determine whether alterations in Na-Pi cotransport specific mRNA and/or protein abundance, versus other regulatory proteins, play a role in the renal tubular adaptation to dietary Pi restriction.