Paracellular pathway

Paracellular pathway refers to the route by which water, ions, and other small molecules pass *between* cells, specifically through the spaces sealed by tight junctions in epithelial or endothelial barriers, rather than through the cells themselves[1][3][5]. Unlike molecular targets such as receptors or transporters, the paracellular pathway is a structural feature regulated by tight junction proteins (including claudins, occludin, tricellulin, and others) that confer selectivity based on size and charge[2][3][6]. This pathway is primarily passive and does not involve saturable or energy-dependent transport—it relies on existing chemical and electrochemical gradients[1][3][5]. Under normal physiological conditions, the paracellular pathway plays a minor role in solute absorption in most mammals, with exceptions in some species (e.g., small birds and bats). It is significantly implicated in pathological contexts: disruption of tight junctions increases paracellular permeability, which is a mechanism in certain gastrointestinal diseases, infections, and can be targeted by some bacterial toxins, resulting in diarrhea and compromised barrier function[2][3][6]. Its function is also important for the oral bioavailability of certain hydrophilic drugs, though only a few drugs primarily use this route, often with low efficiency[1]. Because the paracellular pathway is not a molecular entity and does not fit the definition of a specific "therapeutic target," it is considered incorrect to list it as a drug target[1][5].

Other names

Paracellular transport