title: The rat glomerular filtration barrier does not show negative charge selectivity.
abstract: OBJECTIVE
  To characterize the effects of size, shape, and negative charge on the transport of macromolecules across the glomerular capillary wall by using the sieving curves (fractional clearance vs. solute molecular radii) of fluorescent polydispersed polysaccharide tracers.
  
  
  METHODS
  Glomerular fractional clearances (FC) were measured with fluorescent neutral [isoelectric point (pI) = 7.3 +/- 0.2] and negatively charged (pI = 3.5 +/- 0.4) dextrans (DEX) in comparison with negatively charged (pI = 4.8 +/- 0.3) hydroxy ethyl starch (HES) and (pI = 4.6 +/- 0.1) bovine serum albumin (BSA) in Sprague-Dawley and Fischer 344/Brown Norway rats. FCs (n = 53) were measured by using the urinary clearance of (14)C-inulin to determine the glomerular filtration rate. The relative uptake of each fluorescent probe by endothelial and renal proximal tubule epithelial (LLC-PK(1)) cells, in vitro, was measured microscopically by using a cooled (-25 degrees C) CCD camera.
  
  
  RESULTS
  The sieving curves for randomly coiled neutral and negatively charged DEX probes were identical. These FC values were 6-fold greater than those for HES and 200-fold above similarly sized fluorescent BSA. The polysaccharide probes did not show significant binding to serum proteins. The uptake of BSA by LLC-PK(1) cells was 20- to 100-fold greater than that for neutral or negatively charged macromolecules.
  
  
  CONCLUSIONS
  These findings indicate that the rat glomerular filtration barrier restricts the transport of polysaccharide macromolecules as a function of their size and configuration but not negative charge.
authors.affiliation: Department of Physiology, The University of Arizona, Tucson, AZ, USA. rcschaeffer@earthlink.com
authors.forename: Richard C
authors.initials: RC
authors.lastname: Schaeffer
authors.forename: Max L
authors.initials: ML
authors.lastname: Gratrix
authors.forename: David R
authors.initials: DR
authors.lastname: Mucha
authors.forename: José M
authors.initials: JM
authors.lastname: Carbajal
mesh_terms: D000818:Animals; D000838:Anions; D001692:Biological Transport; D002199:Capillary Permeability; D002460:Cell Line; D003911:Dextrans / Q000493:pharmacokinetics; D004727:Endothelium / Q000166:cytology / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D005919:Glomerular Filtration Rate; D007444:Inulin / Q000652:urine; D007526:Isoelectric Point; D007678:Kidney Glomerulus / Q000098:blood supply* / Q000502:physiology; D008297:Male; D008968:Molecular Conformation; D011134:Polysaccharides / Q000493:pharmacokinetics*; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D012710:Serum Albumin, Bovine / Q000493:pharmacokinetics
chemical_list: D000838:Anions; D003911:Dextrans; D005456:Fluorescent Dyes; D011134:Polysaccharides; D012710:Serum Albumin, Bovine; D007444:Inulin