Membrane controls of epithelial phosphate transport.

Abstract

Phosphate homeostasis involves efficient intestinal absorption of dietary phosphate and sensitive renal conservation of filtered phosphate. Phosphate transport occurs by similar mechanisms across the intestinal and renal epithelium. This includes secondary active uptake across the brush-border membrane, movement of phosphate across the cytosol or into the metabolic phosphate pool, and finally the passive exit from the basolateral membrane. Active transport across the brush-border membrane involves cotransport of phosphate with sodium, which moves down its electrochemical gradient. As this process is the rate-limiting step, it is thought to be the controlling event in intestinal and renal absorption. The interaction of phosphate, sodium, and hydrogen ions with the recognition proteins involved with sodium-dependent phosphate transport is complex and not fully understood. Furthermore, the lipid bilayer structure may play a significant role in controlling the sequence of events in the movement across the brush-border membrane. Transfer of phosphate through the cytosol and exit across the basolateral membrane is less well understood, although the latter transmembrane flux is thought to be carrier mediated. Intestinal phosphate absorption is determined principally by plasma calcium and phosphate concentrations (1,25(OH)2 D3) and dietary availability of phosphate (intrinsic adaptation). On the other hand, renal conservation is determined by the available calcium (PTH), phosphate (intrinsic adaptation), and acid-base balance (hydrogen ions). These controls alter sodium-dependent phosphate cotransport across the brush-border membrane of the epithelial cell. The chemical alterations of the brush-border membrane and the metabolic events leading to changes in the brush-border membrane are not understood. The use of isolated, purified membranes and innovations of current techniques will enhance our understanding of these events and allow us to explain the mechanisms controlling epithelial phosphate absorption.