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Glomerular sieving of three neutral polysaccharides and bikunin in rat. - Effects of molecular size and conformation.

Asgeirsson, Daniel LU ; Venturoli, Daniele LU ; Fries, E; Rippe, Bengt LU and Rippe, Catarina LU (2007) In Acta Physiologica 191(3). p.237-246
Abstract
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 (ae) of the following polymers increases in the order: Ficoll < dextran ≤ 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 (θ) 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... (More)
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 (ae) of the following polymers increases in the order: Ficoll < dextran ≤ 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 (θ) 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 θ for bikunin was measured using a tissue uptake technique.



Results: For a molecule of ae = 55 Å (cf. IgG), θ 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 ae = 36 Å (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). θ for bikunin (0.089 ± 0.0045) was 150 times higher than that of albumin, having an equivalent ae 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Mark-Houwink-Khun-Sakurada, fractional clearance, frictional ratio, capillary permeability
in
Acta Physiologica
volume
191
issue
3
pages
237 - 246
publisher
Wiley-Blackwell
external identifiers
  • wos:000250892700007
  • scopus:35348878790
ISSN
1748-1708
DOI
10.1111/j.1748-1716.2007.01733.x
language
English
LU publication?
yes
id
941a0341-b461-4dee-9c82-3968dd37b25c (old id 1138081)
date added to LUP
2008-08-19 08:42:26
date last changed
2017-08-27 04:06:14
@article{941a0341-b461-4dee-9c82-3968dd37b25c,
  abstract     = {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 (ae) of the following polymers increases in the order: Ficoll &lt; dextran ≤ pullulan &lt; 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 (θ) of the mentioned polymers and of the negatively charged and extended protein bikunin.<br/><br>
<br/><br>
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 θ for bikunin was measured using a tissue uptake technique.<br/><br>
<br/><br>
Results: For a molecule of ae = 55 Å (cf. IgG), θ increased in the order: Ficoll (0.00035 ± 0.000013) &lt; dextran (0.022 ± 0.0029) &lt; pullulan (0.033 ± 0.0024) &lt; PEO (0.12 ± 0.0055). For ae = 36 Å (cf. albumin) the order was: Ficoll (0.076 ± 0.0061) &lt; dextran (0.45 ± 0.037) = pullulan (0.45 ± 0.021) &lt; PEO (0.65 ± 0.0076). θ for bikunin (0.089 ± 0.0045) was 150 times higher than that of albumin, having an equivalent ae and net negative charge.<br/><br>
<br/><br>
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.},
  author       = {Asgeirsson, Daniel and Venturoli, Daniele and Fries, E and Rippe, Bengt and Rippe, Catarina},
  issn         = {1748-1708},
  keyword      = {Mark-Houwink-Khun-Sakurada,fractional clearance,frictional ratio,capillary permeability},
  language     = {eng},
  number       = {3},
  pages        = {237--246},
  publisher    = {Wiley-Blackwell},
  series       = {Acta Physiologica},
  title        = {Glomerular sieving of three neutral polysaccharides and bikunin in rat. - Effects of molecular size and conformation.},
  url          = {http://dx.doi.org/10.1111/j.1748-1716.2007.01733.x},
  volume       = {191},
  year         = {2007},
}