Adaptation to Pi deprivation of cell Na-dependent Pi uptake: a widespread process.
Phosphate enters kidney proximal tubular cells through an apical sodium-phosphate cotransport; this activity (Vmax) increases during phosphate deprivation (Kidney Int. 18: 36-47, 1980). This study investigated the mechanism of phosphate uptake and its adaptation to phosphate deprivation in cultured cells from different origins (kidney, LLC-PK1 and MDCK cells; liver, Fao cells; heart, myocyte primary cultures). All cells exhibited a sodium-dependent phosphate uptake that was reduced (greater than 75%) by external sodium substitution and inhibited by ouabain (35%) and 2,4-dinitrophenol or KCN (80%). Phosphate deprivation (exposure to phosphate-free medium) increased sodium-dependent phosphate uptake by 1.8- to 5.8-fold and decreased cell inorganic phosphate and ATP contents (70-80 and 17-30%, respectively). The stimulation of phosphate uptake resulted from an increase in Vmax without change in Km and was dependent on gene transcription and protein synthesis because it was inhibited by cycloheximide and 3-deoxyadenosine. Thus a deprivation-stimulated, sodium-dependent phosphate transport was demonstrated in cells originating from distal kidney tubules, liver, and heart. The findings suggest that in hypophosphatemic diseases, impairment of renal proximal phosphate reabsorption might be only one expression of a widespread alteration of cell phosphate regulation.
Escoubet
B
B
Institut National de la Santé et de la Recherche Médicale U. 251, Département de Physiologie, Faculté de Médecine X. Bichat, Université Paris 7, France.
Djabali
K
K
Amiel
C
C
D000409:Alanine / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D004140:Dinitrophenols / Q000494:pharmacology; D007700:Kinetics; D009206:Myocardium / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology; D010710:Phosphates / Q000378:metabolism*; D011190:Potassium Cyanide / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000494:pharmacology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D004140:Dinitrophenols; D010710:Phosphates; D010042:Ouabain; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D011190:Potassium Cyanide; D000409:Alanine