Renal apical membrane cholesterol and fluidity in regulation of phosphate transport

B. A. Molitoris, A. C. Alfrey, R. A. Harris, F. R. Simon

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60 Scopus citations


Renal proximal tubule cells adapt to dietary phosphate (P[i]) restriction by increasing P[i] transport independent of parathyroid hormone, vitamin D metabolites, or serum Ca2+. To determine the underlying cellular mechanism(s), brush border (BBM) and basolateral membranes (BLM) were isolated from growing male rats fed a synthetic diet containing variable levels of P[i] (0.1-1.4%). Dietary P[i] restriction was without effect on either BBM or BLM total lipid phosphorus, individual phospholipid species, or BLM Na+-K+-ATPase specific activity. However, dietary P[i] restriction (0.1 vs. 1.0%) did not cause a significant reduction in BBM but not BLM cholesterol (0.45 vs. 0.41μmol/mg protein). Brush border membrane cholesterol was inversely correlated with the tubular reabsorption of P[i] (r = 0.77, P < 0.01) over a broad range (99.9 - 46.2%). Arrhenius analysis of two intrinsic BBM enzymes revealed a significant reduction in the breakpoint temperature for alkaline phosphatase but no change for Mg2+-ATPase. Fluorescence polarization studies showed increased BBM inner core fluidity due to an alteration in neutral lipids but not phospholipid, fatty acid, or protein membrane components. These data demonstrate that the BBM can regulate its cholesterol content independent of the BLM. Furthermore, they suggest that adaptation to dietary P[i] restriction involves a reduction in BBM cholesterol, which may be mediated by an increase in membrane fluidity.

Original languageEnglish (US)
Pages (from-to)F12-F19
JournalAmerican Journal of Physiology - Renal Fluid and Electrolyte Physiology
Issue number1
StatePublished - Dec 1 1985
Externally publishedYes

ASJC Scopus subject areas

  • Physiology

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