Cellular mechanisms in proximal tubular reabsorption of inorganic phosphate.
Filtered inorganic phosphate (Pi) is largely reabsorbed in the proximal tubule. Na-Pi cotransport, with a stoichiometry of at least 2:1, mediates uphill transport at the apical membrane; at the basolateral membrane different types of transport systems can be involved in efflux and uptake of Pi from the interstitium. Regulation of transcellular Pi flux involves alteration of the apical Na-Pi cotransport; at least three different cellular control/sensing systems seem to participate in this regulation and are exemplified by parathyroid hormone (PTH)-dependent inhibition, Pi deprivation-dependent increase, and insulin-like growth factor I (IGF-I)-dependent increase in Na-Pi cotransport. For PTH inhibition, recent evidence suggests a role of the phospholipase C/protein kinase C-dependent regulatory cascade in inhibition of Na-Pi cotransport, at least at low PTH concentrations. In addition, an endocytic mechanism seems to be involved in this PTH action. Little is known of the cellular mechanisms in Pi deprivation-dependent and/or IGF-I-dependent increases in Na-Pi cotransport; they are dependent on de novo protein synthesis. Recent experiments involving an expression in Xenopus laevis oocytes led to the identification of an approximately 50 kDa membrane protein that is a good candidate for being involved in brush-border membrane Na-Pi cotransport activity.
Murer
H
H
Department of Physiology, University of Zurich, Switzerland.
Werner
A
A
Reshkin
S
S
Wuarin
F
F
Biber
J
J
D000042:Absorption; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000502:physiology*; D008954:Models, Biological; D010281:Parathyroid Hormone / Q000494:pharmacology; D010710:Phosphates / Q000378:metabolism*; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters
D002352:Carrier Proteins; D010281:Parathyroid Hormone; D010710:Phosphates; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters; D007334:Insulin-Like Growth Factor I