Renal brush border membrane Na/Pi-cotransport: molecular aspects in PTH-dependent and dietary regulation.
Inorganic phosphate (Pi) is reabsorbed in renal proximal tubules in a sodium (Na)-dependent manner involving brush border Na/Pi-cotransporter(s). Regulation of renal Pi-reabsorption, such as by parathyroid hormone (PTH) and/or by dietary Pi-deprivation, involves alterations in the rate of Na/Pi-cotransport. Two structurally different Na/Pi-cotransporters have been identified: type I-transporter and type II-transporter. The related mRNAs and proteins are located in the proximal tubule and in the brush border membrane. In heterologous expression systems type I and type II Na/Pi-cotransporters mediate Na/Pi-cotransport. Characterization of the transport properties suggested that the type II transporter is "responsible' for brush border membrane Na/Pi-cotransport (as observed in isolated vesicles). Administration of PTH to rats resulted in an inhibition of brush border membrane Na/Pi-cotransport (vesicles) and in a reduced brush border membrane content of the type II transporter. Feeding low Pi-diets resulted in an up-regulation of Na/Pi-cotransport (vesicles) and of type II transporter content; only after a prolonged exposure to low Pi-diets (more than 4 hr) was an increase in specific mRNA content observed. Refeeding high Pi diets had the opposite effects on Na/Pi-cotransport activity and on type II transporter protein. It is currently the task of future experiments to define the specific mechanisms leading to protein-synthesis-independent (PTH, acute Pi-deprivation, Pi-refeeding) and to protein-synthesis-dependent (prolonged Pi-deprivation) regulation of the type II Na/Pi-cotransporter.
Murer
H
H
Institute of Physiology, University of Zürich, Switzerland.
Lötscher
M
M
Kaissling
B
B
Levi
M
M
Kempson
S A
SA
Biber
J
J
D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000502:physiology*; D007668:Kidney / Q000502:physiology* / Q000648:ultrastructure; D008871:Microvilli / Q000737:chemistry / Q000378:metabolism*; D008967:Molecular Biology; D010281:Parathyroid Hormone / Q000502:physiology*; D016226:Phosphorus, Dietary / Q000378:metabolism*; D050608:Sodium-Phosphate Cotransporter Proteins; D050609:Sodium-Phosphate Cotransporter Proteins, Type I; D050610:Sodium-Phosphate Cotransporter Proteins, Type II; D027981:Symporters
D002352:Carrier Proteins; D010281:Parathyroid Hormone; D016226:Phosphorus, Dietary; D050608:Sodium-Phosphate Cotransporter Proteins; D050609:Sodium-Phosphate Cotransporter Proteins, Type I; D050610:Sodium-Phosphate Cotransporter Proteins, Type II; D027981:Symporters