title: Cholesterol modulates rat renal brush border membrane phosphate transport.
abstract: In dietary phosphate (Pi) deprivation and in aging there is an inverse correlation between renal proximal tubular brush border membrane (BBM) cholesterol (Chol) content, BBM fluidity, and BBM sodium gradient-dependent Pi transport activity (Na-Pi cotransport). The purpose of this study was to determine whether in vitro enrichment of renal BBM with Chol has a direct modulating effect on Na-Pi cotransport. 12 and 24 mol % increases in Chol content caused dose-dependent decreases in Na-Pi cotransport activity, 2,000 in control, vs. 1,450 in Chol (+12%), vs. 900 pmol/5 s/mg BBM protein in Chol (+24%), all P less than 0.01, which was paralleled by dose-dependent increases in the fluorescence anisotropy of diphenylhexatriene, rDPH, i.e., decrease in BBM fluidity, 0.203 in control, vs. 0.210 in Chol (+12%), vs. 0.219 in Chol (+24%), all P less than 0.01. We found that increasing ambient temperature, which increases BBM fluidity independent of changes in Chol content, increased Na-Pi cotransport. When Na-Pi cotransport was analyzed as a function of BBM fluidity, 1/rDPH, we found that at an equivalent BBM fluidity BBM Chol enrichment still resulted in a dose-dependent decrease in Na-Pi cotransport. Finally, in BBM isolated from rats fed a low Pi diet in vitro enrichment with Chol completely reversed the adaptive increases in Na-Pi cotransport and fluidity. Our study therefore, indicates that Chol is a direct modulator of renal BBM Na-Pi cotransport activity, and that in vivo alterations in BBM Chol content most likely plays an important role in the regulation of renal tubular Pi transport.
authors.affiliation: Department of Internal Medicine, Dallas Veterans Administration Medical Center, Texas 75216.
authors.forename: M
authors.initials: M
authors.lastname: Levi
authors.forename: B M
authors.initials: BM
authors.lastname: Baird
authors.forename: P V
authors.initials: PV
authors.lastname: Wilson
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism / Q000494:pharmacology*; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D007931:Leucyl Aminopeptidase / Q000378:metabolism; D008297:Male; D008320:Maltose / Q000378:metabolism; D008560:Membrane Fluidity / Q000187:drug effects; D008563:Membrane Lipids / Q000378:metabolism*; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013696:Temperature; D005723:gamma-Glutamyltransferase / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D008563:Membrane Lipids; D010710:Phosphates; D008320:Maltose; D002784:Cholesterol; D005723:gamma-Glutamyltransferase; D000469:Alkaline Phosphatase; D007931:Leucyl Aminopeptidase