Quantitative Approaches To Delineate Paracellular Diffusion in Cultured Epithelial Cell Monolayers

Adson, Anthony; Raub, Thomas J.; Burton, Philip S.; Barsuhn, Craig L.; Hilgers, Allen R.; Audus, Kenneth L.; Ho, Norman F.H.

doi:10.1002/jps.2600831103

Cited by 246 publications

(232 citation statements)

References 32 publications

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“…Paracellular diffusion is limited by the permeability and selectivity of the tight junctions between the epithelial cells [1]. As the electrical resistance of monolayers is determined by the permeability of the tight junctions to ions, then a lower TER indicates an increased permeability to solutes [12].…”

Section: Paracellular Diffusion Of L-glucosementioning

confidence: 99%

Glucose homeostasis across human airway epithelial cell monolayers: role of diffusion, transport and metabolism

Kalsi

Baker

Fraser

et al. 2008

Pflugers Arch - Eur J Physiol

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Glucose in airway surface liquid (ASL) is maintained at low concentrations compared to blood glucose. Using radiolabelled [3 H]-D-glucose and [ 14 C]-Lglucose, detection of D-and L-glucose by high-performance liquid chromatography and metabolites by nuclear magnetic resonance, we found that glucose applied to the basolateral side of H441 human airway epithelial cell monolayers at a physiological concentration (5 mM) crossed to the apical side by paracellular diffusion. Transepithelial resistance of the monolayer was inversely correlated with paracellular diffusion. Appearance of glucose in the apical compartment was reduced by uptake of glucose into the cell by basolateral and apical phloretin-sensitive GLUT transporters. Glucose taken up into the cell was metabolised to lactate which was then released, at least in part, across the apical membrane. We suggest that glucose transport through GLUT transporters and its subsequent metabolism in lung epithelial cells help to maintain low glucose concentrations in human ASL which is important for protecting the lung against infection.

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Section: Paracellular Diffusion Of L-glucosementioning

confidence: 99%

Glucose homeostasis across human airway epithelial cell monolayers: role of diffusion, transport and metabolism

Kalsi

Baker

Fraser

et al. 2008

Pflugers Arch - Eur J Physiol

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“…The binding parameters from the single cell uptake study (Table 1) (1997) 76(7) (Adson et al, 1994(Adson et al, , 1995. The latter have been investigated as models for endothelial or epithelial absorption barriers but, being only one cell thick, do not include the heterogeneous microenvironments that arise as a result of limiting transport of nutrients, oxygen and waste products in the extravascular compartment of tumours.…”

Section: Diffusion Of [3h]dapa Through V79-171 B MMmentioning

confidence: 99%

“…Good reproducibility is seen between replicate determinations, and the estimated DMM is lower than that in medium (compartment 1) by factors of 11 and 8 for V79-171b and EMT6/Ak MM respectively. The flux of urea in this system is British Journal of Cancer (1997) 76(7), [894][895][896][897][898][899][900][901][902][903] 0 Cancer Research Campaign 1997 Drug diffusion in multicellular membranes 901 clearly faster than that across well-differentiated colon carcinoma (Caco-2) cell monolayers (Adson et al, 1994), although the latter are only c. 10 ,um in thickness. The flux of this hydrophilic solute appears to be primarily through a paracellular (between cells) pathway in the latter epithelial model, but a contribution from the transcellular (through cells) pathway cannot be ruled out in V79-171b and EMT6/Ak MM.…”

Section: Diffusion Of [3h]dapa Through V79-171 B MMmentioning

confidence: 99%

An experimental and mathematical model for the extravascular transport of a DNA intercalator in tumours

Hicks

Ohms²,

Zijl³

et al. 1997

Br J Cancer

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9-[3-(N,N-dimethylamino)propylamino]acridine (DAPA) was dramatically slower than urea. Modelling this over the first 5 h gave a DMM of 1.3 x 10-cm2 s-1, but over longer times the kinetics was not consistent with simple diffusion. Flux of DAPA was markedly increased in the presence of 50 mm ammonium chloride, indicating that sequestration in acidic endosomes is a major impediment to flux. Accumulation in cytoplasmic vesicles was confirmed by fluorescence microscopy. The DAPA flux kinetics, with and without ammonium chloride, was well fitted by a reaction-diffusion model with reversible cellular uptake (modelled as binding), using uptake parameters determined in separate experiments with V79-171 b single-cell suspensions. This study demonstrates the utility of the MM model for determining extravascular transport parameters, and indicates that much of the impediment to diffusion of basic DNA intercalators in tumour tissue may arise from lysosomal sequestration rather than DNA binding.

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“…1/P t = 1/P c + 1/P e where P t is the apparent permeability coefficients for the collagen-coated polycarbonate membranes in the presence of BeWo cell monolayers and P c is the apparent permeability coefficients for collagen-coated polycarbonate membranes alone (24).…”

Section: Transmonolayer Permeabilitymentioning

confidence: 99%

Transport and metabolism of opioid peptides across BeWo cells, an in vitro model of the placental barrier

Ampasavate¹,

Chandorkar²,

Velde³

et al. 2002

International Journal of Pharmaceutics

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. (2002) Transport and metabolism of opioid peptides across BeWo Cells, an in vitro model of the placental barrier. Int. J. Pharm. 233,[85][86][87][88][89][90][91][92][93][94][95][96][97][98] Abstract: In keeping with the advance of biotechnology, cell culture becomes an important tool for investigating the transport and the metabolism phenomena. A cell line of human origin, the BeWo choriocarcinoma cell line, was used for the study of the transport and metabolism of opioid peptides across the in vitro model of the placental barrier. Opioid peptides, both naturally occurring and their synthetic analogs, are of interest to be developed as potent analgesics and were included in this study. The apparent permeability coefficients of the peptides containing 4 to 11 amino acid or analog residues were in the range of 0.23-14.60 x 10 -5 cm/sec. The apparent permeability coefficients of these peptides were comparable to those of sucrose or dextrans, hydrophilic markers. Molecular weight and size of the peptides were inversely correlated to the permeability across the BeWo monolayers. Lipophilicity and charges of the peptides were also investigated and found to be the minor factors regulating the extent of peptide permeation. Contrasting to the transport of DPDPE peptide analog across the blood-brain barrier, the transport of DPDPE across the BeWo monolayers were not found to be via carrier-mediated transport. The major transport pathway of the opioid peptides across the BeWo monolayers was found to be via paracellular route. In metabolism studies, aminopeptidase was found to be a major enzyme type responsible for the degradation of naturally occurring peptides but not for the synthetic analogues. The finding obtained from the present study reveal the applicability of the BeWo cell line to be used as the in vitro cell culture model for the transport and metabolism screening of the opioid peptides.

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Quantitative Approaches To Delineate Paracellular Diffusion in Cultured Epithelial Cell Monolayers

Cited by 246 publications

References 32 publications

Glucose homeostasis across human airway epithelial cell monolayers: role of diffusion, transport and metabolism

Glucose homeostasis across human airway epithelial cell monolayers: role of diffusion, transport and metabolism

An experimental and mathematical model for the extravascular transport of a DNA intercalator in tumours

Transport and metabolism of opioid peptides across BeWo cells, an in vitro model of the placental barrier

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