REGULATION OF OPOSSUM KIDNEY (OK) CELL NA/P-I COTRANSPORT BY P-I DEPRIVATION INVOLVES MESSENGER-RNA STABILITY

Renal proximal tubular Na-dependent phosphate transport (Na/P-i cotransport) has been studied extensively in the opossum kidney (OK) cell line. Recently, we cloned a complementary deoxyribonucleic acid (cDNA) (NaPi-4) from OK cells encoding an apical NaPi cotransport system. OK cells exposed to a low-P-i medium, as compared to high-P-i media, responded with an increase in Na/P-i cotransport, which was followed by an increase in NaPi-4 messenger ribonucleic acid (mRNA) abundance; maximal stimulation of Na/P-i cotransport was reached in 2 h, with no further increase for up to 16 h. NAP(i)-4 mRNA abundance was unaltered for 2 h, then increased to a maximum after 6-16 h in cells treated with low Pi medium. NaPi-4 mRNA decay rate was lowered by low-P-i media when compared to high-Pi media, with no increase in the NaPi-4 mRNA transcription rate. These data suggest that the upregulation of Na/P-i cotransport in OK cells by low-Pi media involves two regulatory mechanisms: an immediate (early) increase (after 2 h) in the expression of Na/P-i cotransport, independent of mRNA synthesis or stability, and a delayed (late) effect (after 4-6 h), resulting in an increase in NaPi-4 mRNA abundance, due to an increased stability.