Paracellular permeability regulation

There is growing evidence implicating Na+-dependent solute transporters and intracellular as well as extracellular Ca2+ in the physiological regulation of the paracellular pathway [81,203,204], Such modulation of paracellular permeability is especially important for drugs such as peptides and oligonucleotides that exhibit poor permeability characteristics across both the cornea and the conjunctiva [150,152,154,155], In addition, ion transporters such as Cl and Ca2+ channels have been implicated in macromolecular transport (see Sections IV.B.2 and IV.B.4). In the following discussion, some key ion transport processes and their possible roles in solute transport across epithelial tissues are summarized. 

Gorodeski GI, Hopfer U, De Santis BJ, Eckert RL, Rorke ER, and Utian WH [1995] Biphasic regulation of paracellular permeability in human cervical cells by two distinct nucleotide receptors. Am J Physiol 268 C1215-C1226... 

Gorodeski GI and Hopfer U [1995] Regulation of the paracellular permeability of cultured human cervical epithelium by a purinergic P2-receptor. J Soc Gynecol Investig 2 716-720... 

Gorodeski GI, De Santis BJ, Goldfarb J, Utian WH, and Hopfer H [1995] Osmolar changes regulate the paracellular permeability of cultured human cervical epithelium. Am J Physiol 269 C870-C877... 

Gorodeski GI [2001] Estrogen biphasic regulation of paracellular permeability of cultured human vaginal-cervical epithelia. J Clin Endocrinol Metab 86 4233-4243... 

Baida MS, Flores-Maldonado C, Cereijido M, and Matter K [2000] Multiple domains of occludin are involved in the regulation of paracellular permeability. J Cell Biochem 78 85-96... 

Careful observation at the borders of the enterocytes reveals a close juxtaposition of the membranes of adjacent epithelial cells, identified as zonulae occludens, located at the apical neck of the epithelial cells [168], The zonulae occludens is composed of apical complex the tight junctions and more basal structure underneath, the adherens junctions (also referred to as intermediate junctions) [169,170]. The adherens junctions are linked to the actomyosin ring at the cell circumference. This actin cytoskeleton, which forms a perijunctional area at the apical neck of the epithelial cells, is the cause for their polarized nature (Figure 1.12). The classical functions of tight junctions are the regulation of paracellular permeability and the restriction of apical basolateral intramembrane diffusion of lipids (cell polarity housekeeping). 

Turner, J.R. 2000. Show me the pathway Regulation of paracellular permeability by Na+-glucose cotransport. Adv Drug Deliv Rev 41 265. 

The adherent junctions are ubiquitously found in the cerebral vasculature and mediate several functions, including the adhesion of endothelial cells to each other, contact inhibition during remodeling, and growth of the vasculature, and mediate in part the regulation of paracellular permeability (Hawkins and Davis, 2005). The most important components of the adherent junctions are vascular endothelial... 

VE)-cadherin and platelet endothelial cell adhesion molecule-1 (PECAM-1). VE-cadherin is an endothelial-specific Ca " -regulated protein that is linked to the cytoskeleton via catenins (Fig. 1). PECAM-1, also known as CD31, is a key participant in the migration of blood-borne cells across the BBB. Changes in the adherent junction proteins can lead to increased paracellular permeability (Abbruscato and Davis, 1999) and leukocyte trafficking in the CNS (Newman, 1994 Garrido-Urbani et al., 2008). 

Anderson, J.M. van Itallie, C.M. Tight junctions and the molecular basis for regulation of paracellular permeability. Am. J. Physiol. 1995, 269 (32), G467-G475. 

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