AIM: Polysaccharides and many other non-protein polymers generally have a more open, flexible and asymmetrical structure compared with globular proteins. For a given molecular weight (MW), the Stokes-Einstein radius (a(e)) of the following polymers increases in the order: Ficoll < dextran <or= pullulan < polyethylene oxide (PEO). We have tested the hypothesis that such an increase in 'molecular extension' will increase the molecule's glomerular permeability. Thus, we investigated the glomerular sieving coefficients (theta) of the mentioned polymers and of the negatively charged and extended protein bikunin. METHODS: In anaesthetized Wistar rats, glomerular sieving curves were generated for each FITC-labelled polymer from their respective concentration in urine and plasma, determined by size exclusion chromatography. The theta for bikunin was measured using a tissue uptake technique. RESULTS: For a molecule of a(e) = 55 A (cf. IgG), theta increased in the order: Ficoll (0.00035 +/- 0.000013) < dextran (0.022 +/- 0.0029) < pullulan (0.033 +/- 0.0024) < PEO (0.12 +/- 0.0055). For a(e) = 36 A (cf. albumin) the order was: Ficoll (0.076 +/- 0.0061) < dextran (0.45 +/- 0.037) = pullulan (0.45 +/- 0.021) < PEO (0.65 +/- 0.0076). theta for bikunin (0.089 +/- 0.0045) was 150 times higher than that of albumin, having an equivalent a(e) and net negative charge. CONCLUSION: From these results it is concluded that for flexible and asymmetric macromolecules, their degree of glomerular hyperpermeability is proportional to their degree of 'molecular extension'. Thus, compared with globular proteins, the polysaccharides investigated, including Ficoll, were found to be hyperpermeable across the glomerular filter in vivo.
AIM: Polysaccharides and many other non-protein polymers generally have a more open, flexible and asymmetrical structure compared with globular proteins. For a given molecular weight (MW), the Stokes-Einstein radius (a(e)) of the following polymers increases in the order: Ficoll < dextran <or= pullulan < polyethylene oxide (PEO). We have tested the hypothesis that such an increase in 'molecular extension' will increase the molecule's glomerular permeability. Thus, we investigated the glomerular sieving coefficients (theta) of the mentioned polymers and of the negatively charged and extended protein bikunin. METHODS: In anaesthetized Wistar rats, glomerular sieving curves were generated for each FITC-labelled polymer from their respective concentration in urine and plasma, determined by size exclusion chromatography. The theta for bikunin was measured using a tissue uptake technique. RESULTS: For a molecule of a(e) = 55 A (cf. IgG), theta increased in the order: Ficoll (0.00035 +/- 0.000013) < dextran (0.022 +/- 0.0029) < pullulan (0.033 +/- 0.0024) < PEO (0.12 +/- 0.0055). For a(e) = 36 A (cf. albumin) the order was: Ficoll (0.076 +/- 0.0061) < dextran (0.45 +/- 0.037) = pullulan (0.45 +/- 0.021) < PEO (0.65 +/- 0.0076). theta for bikunin (0.089 +/- 0.0045) was 150 times higher than that of albumin, having an equivalent a(e) and net negative charge. CONCLUSION: From these results it is concluded that for flexible and asymmetric macromolecules, their degree of glomerular hyperpermeability is proportional to their degree of 'molecular extension'. Thus, compared with globular proteins, the polysaccharides investigated, including Ficoll, were found to be hyperpermeable across the glomerular filter in vivo.
Authors: Hemant Sarin; Ariel S Kanevsky; Haitao Wu; Kyle R Brimacombe; Steve H Fung; Alioscka A Sousa; Sungyoung Auh; Colin M Wilson; Kamal Sharma; Maria A Aronova; Richard D Leapman; Gary L Griffiths; Matthew D Hall Journal: J Transl Med Date: 2008-12-18 Impact factor: 5.531