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The Paracellular Pathway

1993; Springer Nature; Linguagem: Inglês

10.1007/978-1-4615-2898-2_1

1078-0467

Marcelino Cereijido, Octavio Ruiz, Lorenza González‐Mariscal, R. Contreras, María S. Balda, Refugio García‐Villegas,

S100 Proteins and Annexins

The paracellular pathway is an aqueous, extracellular route across endothelia and epithelia that is followed by substances according to their size and charge. Although under certain circumstances it may be traversed by objects as large as leukocytes, it is generally used by water and small solutes. Under normal circumstances, proteins can only permeate through endothelia and a few types of epithelia, such as the glomerular and choroidal ones (Renkin and Gilmore, 1973; Kluge et al., 1986). It is limited by a tight junction (TJ) placed at the outermost end of the intercellular space (Fig. 1). Since this structure was first—and for many years—studied in epithelia like the frog skin and the urinary bladder, where it almost completely obstructs the passage of all substances, it is usually called a "tight" or "occluding" junction. In epithelia that separate two compartments with different compositions (e.g., the frog skin, the colon mucosa, the kidney collecting tubule), the TJ is in fact very restrictive and the amount of substances flowing through the paracellular pathway is almost negligible. On the contrary, in epithelia separating two compartments with similar ionic composition, and that have to translocate a relatively large volume of fluid in a short time (e.g., the kidney proximal tubule, the gallbladder mucosa), the TJ is quite leaky and the paracellular pathway may account for up to 90% of the transepithelial flux. When the TJ is so leaky, the rate of permeation through the paracellular pathway may also be restricted by the narrowness and tortuosity of the intercellular space, as well as by the composition of the extracellular matrix (Cereijido, 1991).