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Updated: Jul 17, 2026

Models and Methods to Evaluate Transport of Drug Delivery Systems Across Cellular Barriers
Published on: October 17, 2013
Coupling between apical and paracellular transport processes
1The St. Michael's Hospital Research Institute and Department of Surgery, University of Toronto, 30 Bond Street, Queen Wing 7009, Toronto, ON M5B 1W8, Canada.
Transcellular transport impacts paracellular flux by altering epithelial barrier permeability. Myosin contractility links apical transporters to paracellular pathway regulation, with cell-specific signaling mechanisms.
Area of Science:
- Epithelial physiology
- Cellular biology
- Molecular mechanisms
Background:
- Transcellular transport influences paracellular flux via driving force and permeability.
- Coordination prevents large electrical and osmotic gradients during transepithelial transport.
- Apical transporters' effects on paracellular pathways remain incompletely understood.
Purpose of the Study:
- To review current knowledge on paracellular permeability regulation.
- To explore the link between apical Na+-glucose cotransport and myosin phosphorylation.
- To discuss cell-specific signaling mechanisms involved.
Main Methods:
- Literature review of recent studies on tight junctions and epithelial barriers.
- Analysis of signaling pathways connecting apical transport to myosin phosphorylation.
- Comparison of proposed mechanisms in intestinal and kidney cells.
Main Results:
- Myosin-based contractility is central to coupling apical transporters with paracellular permeability.
- Myosin phosphorylation's role is universal, but triggering mechanisms are cell-specific.
- Intestinal cells: p38 MAP kinase-induced alkalinization via Na+/H+-exchanger.
- Kidney cells: Na+-cotransport-triggered depolarization leading to Rho-mediated myosin phosphorylation.
Conclusions:
- Apical transporters regulate paracellular permeability through myosin-based contractility.
- Signaling pathways are cell-specific, involving kinase cascades or membrane potential changes.
- Understanding these mechanisms is crucial for epithelial barrier function.
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