Glomerular sieving of three neutral polysaccharides and bikunin in rat. - Effects of molecular size and conformation.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1138081
- author
- Asgeirsson, Daniel LU ; Venturoli, Daniele LU ; Fries, E ; Rippe, Bengt LU and Rippe, Catarina LU
- organization
- publishing date
- 2007
- 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
- 2016-04-01 12:08:39
- date last changed
- 2022-03-13 05:55:46
@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 < 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.<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) < 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.<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}}, keywords = {{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}}, doi = {{10.1111/j.1748-1716.2007.01733.x}}, volume = {{191}}, year = {{2007}}, }