A molecular view of proximal tubular inorganic phosphate (P-i) reabsorption and of its regulation

In recent years, two mammalian proximal tubular brush border membrane Na/P-i cotransporters (types I and II) have been structurally identified by expression cloning techniques. Oocyte expression studies have shown that only the transport characteristics of the type LI transporter correspond to the well-known properties of proximal tubular brush border membrane of Pi transport. In studies on physiological regulation by hormonal and non-hormonal factors a direct involvement and determining role of the type II transporter has been documented. Most interestingly, specific membrane retrieval/insertion phenomena participate in acute (minutes/hours) adjustments of brush border membrane Na/P-i cotransport rates; for chronic (hours/days) alterations also specific resynthesis/degradation processes participate. In pathophysiological alterations (e.g. in X-linked hypophosphataemia and in heavy metal-induced nephrotoxicity) the expression of the type LT Na/P-i cotransporters is reduced and explains the observed phosphaturia.