Homer Smith Award. Cellular mechanisms in proximal tubular Pi reabsorption: some answers and more questions.
Inorganic phosphate (Pi) is reabsorbed mainly in the proximal tubule, by a second active Na-dependent transport mechanism. Na/Pi cotransport with a stoichiometry exceeding unity mediates uphill flux across the brush border membrane; at the basolateral cell surface, two separate transport systems are involved in equilibrating Pi fluxes. The protein structure of a rabbit renal cortex Na/Pi cotransport system has been identified recently by expression cloning. The regulation of tubular Pi reabsorption involves mainly alterations in the transport rate of the brush border membrane Na/Pi cotransport system. The regulation of this transport step by either parathyroid hormone (PTH) or Pi deprivation is discussed, mostly on the basis of observations made with a tissue culture model, OK cells derived from opossum kidney. In this model, PTH may use a dual signaling cascade to inhibit apical Na/Pi cotransport (phospholipase C/protein kinase C and adenylate cyclase/protein kinase A). PTH action on Na/Pi cotransport may involve an endocytosis mechanism. For the regulation of apical Na/Pi cotransport by chronic Pi deprivation, the number of "Na/Pi cotransporter" molecules seems to be unaffected; the increased transport rate is apparently related to an "unknown" stimulating event at the membrane level (e.g., a change in the lipid microenvironment), which itself is under the control of protein synthesis/degradation. The availability of new tools (cloning of Na/Pi cotransporter(s) and of PTH receptor(s)) will allow us to enter into a new era in the study of cellular mechanisms involved in proximal tubular Pi reabsorption.
Murer
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Physiologisches Institut, Universität Zürich, Switzerland.
D000818:Animals; D001363:Awards and Prizes; D001693:Biological Transport, Active; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism*; D008954:Models, Biological; D009398:Nephrology; D009518:New York; D010281:Parathyroid Hormone / Q000494:pharmacology; D010710:Phosphates / Q000378:metabolism*; D012955:Societies, Medical; D012964:Sodium / Q000378:metabolism
D010281:Parathyroid Hormone; D010710:Phosphates; D012964:Sodium