Membrane permeability as a cause of transport defects in experimental Fanconi syndrome. A new hypothesis.
The injection of sodium maleate (200-400 mg/kg) into rats produces aminoaciduria along with glycosuria and phosphaturia, resembling the Fanconi syndrome. This experimental model was studied by means of microinjections into proximal convoluted tubules of the kidney, stop-flow diuresis, and microperfusion of single nephrons. Our results show that, in maleate-treated rats, competition between amino acids or related structures (L-proline, L-OH-proline, and glycine) possesses the same characteristics, and net influx of amino acids appear normal at the proximal nephron. Data obtained by classical stop-flow techniques and single nephron microperfusions also indicate a normal entry of labeled amino acids (L-lysine, glycine, L-valine, L-proline, L-cystine), and 3-0-methyl-D-[3H]glucose and [32P]phosphate from the luminal side of the proximal tubule cell. However, the efflux of molecules from the cell appears enhanced throughout the proximal and distal tubule; molecules that exit at this site are excreted directly into the urine. Our results suggest that the phosphaturia, aminoaciduria, and glycosuria of the experimental Fanconi syndrome can be explained by a modification of the cell membrane permeability (increased efflux) at distal sites of the nephron rather than by a modification of the membrane transport (decreased influx) at the proximal sites, as is currently accepted. Our data also stress the importance of efflux phenomena in membrane transport.
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D001693:Biological Transport, Active; D002462:Cell Membrane / Q000378:metabolism*; D002463:Cell Membrane Permeability; D004195:Disease Models, Animal; D005198:Fanconi Syndrome / Q000139:chemically induced / Q000378:metabolism*; D005260:Female; D007328:Insulin / Q000378:metabolism; D007684:Kidney Tubules / Q000378:metabolism*; D008298:Maleates; D008757:Methylglucosides / Q000378:metabolism; D008845:Microinjections; D008954:Models, Biological; D010710:Phosphates / Q000378:metabolism; D051381:Rats
D000596:Amino Acids; D007328:Insulin; D008298:Maleates; D008757:Methylglucosides; D010710:Phosphates