The Handling of Macromolecules by the Kidney of the River Lamprey, Lampetra Fluviatilis

1981 ◽  
Vol 93 (1) ◽  
pp. 303-316
Author(s):  
A. G. Logan ◽  
R. Morris

Micropuncture and renal clearance techniques have been used to investigate the effect of molecular size on glomerular permeability in the river lamprey, Lampetra fluviatilis, and to investigate tubular absorption of native and foreign macromolecules. Polyvinyl pyrrolidone (PVP) molecules of 16 Å in molecular radius were freely filterable but there was significant retention of 37 Å molecules. The estimated sieving coefficients for PVP of 160 000 and 360 000 in molecular weight (molecular radii > 100 Å) were 0.06 and 0.01 respectively, indicating that the glomerular barrier is relatively leaky. Up to 50% of microinjected protein was absorbed by the nephron and the results with bovine serum albumin demonstrated that protein uptake occurs chiefly in the proximal brush border segment. The relative rates of uptake for different proteins and different concentrations of injected solutions indicated that the uptake mechanism is easily saturated and unable to distinguish between native and foreign proteins of high molecular weight. Most lamprey plasma proteins are > 100 000 in molecular weight. This, together with other factors such as molecular charge and tubular reabsorption, could account for the low urinary protein concentration of 0.05 mg/ml.

2005 ◽  
Vol 288 (4) ◽  
pp. F605-F613 ◽  
Author(s):  
Daniele Venturoli ◽  
Bengt Rippe

Polydisperse mixtures of dextran or Ficoll have been frequently used as molecular probes for studies of glomerular permselectivity because they are largely inert and not processed (reabsorbed) by the proximal tubules. However, dextrans are linear, flexible molecules, which apparently are hyperpermeable across the glomerular barrier. By contrast, the Ficoll molecule is almost spherical. Still, there is ample evidence that Ficoll fractional clearances (sieving coefficients) across the glomerular capillary wall (GCW) are markedly higher than those for neutral globular proteins of an equivalent in vitro Stokes-Einstein (SE) radius. Physical data, obtained by “crowding” experiments or measurements of intrinsic viscosity, suggest that the Ficoll molecule exhibits a rather open, deformable structure and thus deviates from an ideally hard sphere. This is also indicated from the relationship between (log) in vitro SE radius and (log) molecular weight (MW). Whereas globular proteins seem to behave in a way similar to hydrated hard spheres, polydisperse dextran and Ficoll exhibit in vitro SE radii that are much larger than those for compact spherical molecules of equivalent MW. For dextran, this can be partially explained by a high-molecular-size asymmetry. However, for Ficoll the explanation may be that the Ficoll molecule is more flexible (deformable) than are globular proteins. An increased compressibility of Ficoll and an increased deformability and size asymmetry for dextran may be the explanation for the fact that the permeability of the GCW is significantly higher when assessed using polysaccharides such as Ficoll or dextran compared with that obtained using globular proteins as molecular size probes. We suggest that molecular deformability, besides molecular size, shape, and charge, plays a crucial role in determining the glomerular permeability to molecules of different species.


1966 ◽  
Vol 124 (6) ◽  
pp. 1123-1134 ◽  
Author(s):  
Richard C. Graham ◽  
Morris J. Karnovsky

1. Glomerular permeability was studied by ultrastructural cytochemistry, using as protein tracers two intravenously injected peroxidases of differing molecular weight. 2. Horseradish peroxidase (molecular weight 40,000) passed rapidly through the endothelial fenestrae, across the basement membrane, and through the epithelial slits into the urinary space. Human myeloperoxidase (molecular weight 160,000 to 180,000) also passed rapidly through the endothelial fenestrae and across the basement membrane, but was impeded at the level of the epithelial slits. Both proteins were taken up in large amounts by the mesangial cells. 3. The present findings indicate that the epithelial slits are the primary filtration barrier responsible for the differential permeability to proteins of varying molecular size. 4. The observations also support the concept that an important function of the mesangial cells is the incorporation and disposal of glomerular filtration residues.


1966 ◽  
Vol 16 (03/04) ◽  
pp. 384-394 ◽  
Author(s):  
S Cronberg ◽  
B Robertson ◽  
Inga Marie Nilsson ◽  
J.-E Niléhn

Summary43 normal volunteers, 3 patients with thrombophlebitis, and 1 patient with a high platelet adhesiveness and a history of thrombophlebitis have received dextran and its action on the mechanism of haemostasis has been studied. Platelet adhesiveness has been investigated by a slight modification of Hellem’s methods for whole blood and plasma. Dextran with a mean molecular weight of 70,000 produced a markedly lowered platelet adhesiveness together with a moderate prolongation of the Ivy bleeding time. Factor VIII was decreased by about 50% and factor V, factor IX and fibrinogen were decreased slightly more than could be expected from haemodilution alone. No fibrinolysis occurred. Dextran of lower molecular size was less potent. The possible use of dextrans as a thrombosis prophylactic agent is discussed.


2019 ◽  
Vol 59 (5) ◽  
pp. 805-809 ◽  
Author(s):  
V. K. Golovanov ◽  
N. S. Nekrutov ◽  
A. O. Zvezdin ◽  
A. K. Smirnov ◽  
I. A. Tsimbalov

Soil Research ◽  
1969 ◽  
Vol 7 (3) ◽  
pp. 229 ◽  
Author(s):  
JHA Butler ◽  
JN Ladd

Humic acids extracted from soil with sodium pyrophosphate have greater proportions of lower molecular weight material, less acid-hydrolysable amino acid nitrogen contents, but greater carboxyl contents and extinction values (260 and 450 nm) than humic acids extracted subsequently from the same sample with alkali. Humic acids extracted with alkali from fresh soil samples have intermediate values. Extinction values at 260 nm are directly correlated with carboxyl contents for a given soil. Different crop histories have no significant effect on the measured properties of the extracted humic acids. An alkali-extracted humic acid has been fractionated by gel filtration into seven fractions of different nominal molecular weight ranges. As the molecular weights of the fractions increase, both aliphatic C-H (based on infrared absorption at 2900 cm-1) and acid-hydrolysable amino acid contents increase, whereas extinction values at 260 nm and carboxyl contents decrease. The infrared spectra of the high molecular weight fractions have peaks at 1650 and 1510 cm-1 which correlate with acid-hydrolysable amino acid contents and which correspond to amide I and II bands of peptide bonds. Alkaline hydrolysis to split peptide bonds eliminates both these peaks. The spectra also have peaks at 1720 and 1210 cm-1 which correlate with the carboxyl content.


1974 ◽  
Vol 137 (1) ◽  
pp. 123-125 ◽  
Author(s):  
S. R. Levinson ◽  
J. C. Ellory

The molecular size of acetylcholinesterase (EC 3.1.1.7) from the electric organ of Electrophorus electricus and erythrocyte ‘ghosts’ was estimated in both membrane-bound and purified preparations by irradiation inactivation. Results suggest that the form of the enzyme in the membrane is a monomer of molecular weight approx. 75000 and that multiple forms of the enzyme observed in solubilized preparations are aggregates of this monomer.


1975 ◽  
Vol 28 (1) ◽  
pp. 189 ◽  
Author(s):  
RA Shanks

Gel permeation columns of Bio Beads S-X8 have been used to provide separation of oligomers and other small organic molecules. Results show successful separations up to molecular weight c. 600. The retention times of compounds have been correlated with the largest molecular dimension of the molecules and also with molar volumes.


2004 ◽  
Vol 91 (05) ◽  
pp. 927-934 ◽  
Author(s):  
Vivian Douros ◽  
Thomas Podor ◽  
Stephen Shaughnessy ◽  
Jeffrey Weitz ◽  
Edward Young

SummaryUnfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) are cleared, at least in part, by the kidneys through a poorly understood process. This study was undertaken to explore the mechanism of renal clearance of these drugs. Rats were given fluorescein-5-isothiocyanate (FITC)-labeled UFH or LMWH intravenously. At intervals after injection, rats were euthanized and the kidneys were harvested and subjected to immunohistochemical analysis and fluorescence microscopy. Both UFH and LMWH were localized to renal tubular cells and no immunoperoxidase staining or fluorescence was detected in glomeruli. Autoradiography demonstrated similar intracellular distribution of radio-labeled UFH suggesting that this phenomenon is independent of the method used to label heparin. Fluoresence in the tubules increased as a function of time after UFH injection, but reached a plateau after LMWH injection suggesting that the rate of renal tubular uptake depends on the molecular size of the heparin. When administered prior to FITC-labeled UFH or LMWH, probenecid, a renal organic anion inhibitor, decreased the renal tubular uptake of the heparins, whereas cimetidine, a renal organic cation inhibitor, had no effect. These findings suggest that renal excretion of UFH and LMWH primarily reflects tubular uptake via an organic anion transport mechanism.


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